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Review

Medical Scope of Biofilm and Quorum Sensing during Biofilm Formation: Systematic Review

by
Mulat Erkihun
1,*,
Zelalem Asmare
2,
Kirubel Endalamew
3,
Birhanu Getie
1,
Teklehaimanot Kiros
1 and
Ayenew Berhan
1
1
Department of Medical Laboratory Sciences, College of Health Sciences, Debre Tabor University, Debre Tabor P.O. Box 272, Ethiopia
2
Department of Medical Laboratory Sciences, College of Health Sciences, Woldia University, Woldia P.O. Box 400, Ethiopia
3
Department of Diagnostic Laboratory at Shegaw Motta General Hospital, East Gojjam, Motta Town P.O. Box 50, Ethiopia
*
Author to whom correspondence should be addressed.
Bacteria 2024, 3(3), 118-135; https://doi.org/10.3390/bacteria3030008
Submission received: 3 April 2024 / Revised: 17 June 2024 / Accepted: 19 June 2024 / Published: 24 June 2024
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Abstract

:
Biofilms are accumulations of microorganisms in an extracellular polymeric substance matrix which are composed of polysaccharides, proteins, lipids, and nucleic acids. Many bacteria can switch between a planktonic form and a biofilm form. The planktonic bacteria have relatively high cell growth and reproduction rates and have a reduced likelihood of survival but can adapt to occupy new habitats. The biofilm state appears to be a natural and predominant state of bacteria. The need for the formation of bacterial biofilm is that it enhances the tolerance of bacteria to harsh environmental conditions, thereby allowing bacteria to avoid being washed away by water flow or the bloodstream by simply attaching to a surface or tissue, and the EPS matrix protects bacteria cells, in deeper layers, against antimicrobial agents, probably by limiting the diffusion of these agents. Biofilm formation steps are initial contact/attachment to the surface, followed by micro-colony formation, maturation and formation of the architecture of the biofilm, and finally detachment/dispersion of the biofilm. Once formed, biofilm restricts bacterial mobility and increases cell density. Secretions of autoinducers into the environment are critical for cross-signaling between bacteria. This cross-talk is called quorum sensing (QS). Quorum sensing is a cell–cell communication mechanism between bacteria that allows specific processes to be controlled, such as biofilm formation and virulence factor expression. Bacterial quorum sensing signaling mainly consists of acyl-homoserine lactones (produced by Gram-negatives), autoinducing peptides (produced by Gram-positives), and autoinducer-2 (produced by both Gram-negatives and Gram-positives). Therefore, this review is aimed at how bacterial biofilms work and are formed.

1. Introduction

The discovery of biofilms can be traced back to Anthony van Leeuwenhoek’s observation of surface-associated bacteria in 1684. However, the term “biofilm” was officially introduced and defined in a paper by Costerton et al. in 1978. In 1993, the American Society for Microbiology recognized the significance of biofilms as structured communities of bacterial cells enclosed in a self-produced polymeric matrix adherent to surfaces. This matrix, comprising polysaccharides, proteins, and DNA, acts as a protective barrier shielding bacteria from various environmental stresses [1,2,3].
Quorum sensing (QS), a form of cell-to-cell communication, involves the synthesis and release of signaling molecules called autoinducers by bacteria. As the bacterial population density increases, the concentration of these signaling chemicals rises, prompting bacteria to respond collectively once a minimum threshold concentration is reached. QS hastens bacteria to regulate behaviors such as biofilm formation and pathogenicity in a synchronized manner based on species complexity and cell density. This communication mechanism allows bacteria to switch between individual antisocial behavior at low cell density and collective community behavior at high cell density. Bacterial QS systems share fundamental methods for identifying and responding to changes in bacterial cell numbers, facilitating adaptation to environmental variations. Moreover, QS is a crucial mechanism in bacterial communication where signaling molecules called autoinducers mediate interactions within bacterial populations. This density-dependent process allows bacteria to coordinate and function as a unified group, regulating various functions such as secondary metabolite production, sporulation, biofilm formation, and symbiosis [4,5,6].
The three fundamental principles of bacterial QS include, firstly, concentration-dependent response to autoinducers that autoinducers release outside the bacterial cell, and their effects are influenced by their concentration levels, triggering specific responses within the bacterial community; secondly, specialized receptors that bacteria possess in their cell membrane or cytoplasm that can detect and respond to the concentration of autoinducers, allowing for the initiation of QS pathways; and lastly, the activation of the QS loop, of which the detection of autoinducers by receptors initiates the QS loop, leading to the regulation of bacterial virulence factors and behaviors [7].
For many medically significant bacteria, including Pseudomonas aeruginosa (P. aeruginosa), Escherichia coli (E. coli), and Staphylococcus aureus (S. aureus), biofilm formation is a key mechanism of virulence in their pathogenesis. Numerous illnesses are linked to or caused by biofilm infections, such as otitis, conjunctivitis, vaginitis, colitis, pneumonia (ventilator-related), gingivitis, and urethritis. In fact, it is estimated that biofilms directly cause around 80% of all microbial infections in people, and treating these diseases associated with biofilms costs more than USD 1 billion a year. P. aeruginosa biofilms in the lungs of patients with cystic fibrosis are one biofilm-related infection that is very concerning to medical professionals. An opportunistic bacterium called P. aeruginosa has been linked to both acute and chronic lung infections, which can have a serious negative impact on morbidity and death [7,8].
Chronic wound infections are another area of great concern. Over 80% of the 100,000 limb amputations performed on patients with diabetes annually are thought to be the result of extremely persistent biofilm-related wound infections, which mostly include the bacteria P. aeruginosa and S. aureus [7].
Implanted medical devices are another crucial area to take into account when thinking about biofilm and biofilm-related infections. While these implanted medical devices, which can include orthopedic implants, pacemakers, urine catheters, heart valves, stents, and intravascular catheters, are frequently employed to save lives, biofilm colonization can pose a serious risk to patient safety [1]. Both Gram-positive and Gram-negative bacteria have the ability to grow into biofilms on medical equipment, which can be fatal and result in chronic infections, device failure, and high rates of morbidity and death [1]. The most frequently occurring bacteria that are known to create biofilms on medical devices are S. aureus, Staphylococcus epidermidis (S. epidermidis), Streptococcus viridians (S. viridans), E. coli, Klebsiella pneumoniae (K. pneumoniae), Enterococcus faecalis (E. faecalis), Proteus mirabilis (P. mirabilis), and P. aeruginosa. S. aureus and S. epidermidis are assumed to be the origin of 40–50% of prosthetic heart valve infections, 50–70% of catheter biofilm infections, and 87% of bloodstream infections [1]. In addition, the chance of contracting an infection linked to the catheter rises by around 10% every day it is in place [9].
According to estimates, biofilms are the source of between 65% and 80% of all microbial illnesses in hospitals that affect humans. Because biofilm infections are resistant to being removed by host defense systems and antimicrobials, once they are developed, they are particularly difficult to eradicate [10,11].
The majority of existing antimicrobial treatments are typically created and assessed against bacteria that are in the free-living (planktonic) phase of life. As a result, pathogenic biofilms, which are up to 1000 times more resistant to antibiotic treatments, are typically unaffected by these treatments [7]. They are extremely challenging to successfully treat and remove due to the phenomenon of biofilm recalcitrance. Therefore, there is an urgent need for innovative approaches to biofilm treatment, dispersal, and prevention. An overview of bacterial biofilm production, QS, signaling mechanisms, and the current approaches to biofilm removal, control, and prevention are presented in this session.

2. Methods

A literature search was conducted on PubMed to identify all published or electronically published English-language articles relevant to biofilm, QS, and cross-talk in bacteria; a total of 96 records from 2014 to 2023 were included. The Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) methodology was employed for the literature search and selection. The search was carried out for clinical trials, systematic reviews, reviews, randomized controls, and research articles, which could be relevant information sources for this work. In PubMed, the following search string was used: ((“Biofilm and Quorum Sensing” [Mesh]) OR (Biofilm)) AND (((“Quorum Sensing” [Mesh]) OR (biofilm)) OR (biofilms)). For articles that included biofilm and QS, further screening was carried out. The article exclusion criteria used were text not in English, biofilms other than medical aspects, and biofilm and QS in other than bacteria (candida species and others) (Figure 1).

3. Biofilm Formation

A biofilm is a collection of microbial cells that are attached to surfaces and are encased in an extracellular matrix of polymeric substances. It is a synergetic community of microorganisms in which bacterial cells stick to each other and behave as microbial social [12,13].
Biofilm formation is a complex process that depends on various environmental factors (surface porosity, fluid flow, nutrient availability, etc.). Extracellular polysaccharide matrix (EPS) has a significant role in biofilm formation. Molecular genetic studies on P. aeruginosa showed that activation of genes necessary for extracellular polysaccharide synthesis took place after establishing a stable connection between bacteria and the substrate surface [12].
Biofilms will form on almost any material where nutrients are available, but it is more likely to happen if the attachment surface is rough, scratched, cracked, or corroded. Physical conditions, such as hydrophobicity, surface electrostatic charge, and fluid flow rate, also affect the attachment. Several studies have shown that microorganisms attach more rapidly to hydrophobic, nonpolar surfaces such as Teflon and other plastics than to hydrophilic surfaces like stainless steel, so some kind of hydrophobic interaction apparently occurs, which enables the cells to overcome the repulsive forces [13].
Unattached free-swimming bacteria (planktonic) initially attach to a solid surface, eventually maturing into structured aggregates called micro-colonies. Biofilms are composed of these micro-colonies, often encased in extracellular polymeric substances known as the matrix. Some biofilm bacteria detach from microcolonies and become planktonic, presumably colonizing a new surface [14].
Biofilm formation occurs in a few common steps controlled by (QS): initial contact/attachment to the surface, followed by micro-colony formation, maturation and formation of the architecture of the biofilm, and finally, detachment/dispersion of the biofilm [12]. The diagram representation of biofilm formation is shown as in Figure 2.

4. Initial Attachment to the Surface

In this step of biofilm formation, microbial cells attach to the biotic or abiotic surface by using their appendages like pilli and flagella and via other physical forces like van der Waal’s forces, electrostatic interactions, etc. Two types of attachment occur in this step: adhesion—the attachment of microbial cells to a surface, and cohesion—the interaction/attachment within the cells [14]. The flagella, fimbriae, and Pilli give strength to the interaction between bacteria and the surface of attachment. In addition, the hydrophobic nature of the surface also plays a role in strengthening the attachment of microbes by reducing the force of repulsion between the bacteria and the surface [16,17]. Studies have reported the involvement of QS in the initial stages of biofilm development, attachment, and mobility. In P. aeruginosa, QS becomes active during irreversible attachment. In human Helicobacter pylori and Salmonella typhimurium, QS may also be involved in the attachment phase via the luxP gene regulator. (luxP is a gene coding for the extensive protein family known as periplasmic binding proteins (PBPs). These proteins are important binding sites for ligands of biofilm formation and are classically called autoinducers [18].

5. Micro-Colony Formation

After microorganisms attach to a biotic or an abiotic surface and this attachment becomes stable, a process of multiplication of microbial cells starts and the formation of the EPS matrix fixes the initial adhesion. This process of division then leads to the formation of micro-colonies [17]. Microbial colonies in a biofilm usually consist of many types of micro-communities that coordinate with one another in multiple aspects. The exchange of substrate, the distribution of significant metabolic products, and the excretion of metabolic end products are all significantly impacted by this coordination. For example, when complex organic matter is transformed into CH4 and CO2 during anaerobic digestion, at least three different species of bacteria must be involved: (i) Fermentative bacteria begin converting organic molecules into acid and alcohol. (ii) These products are, in turn, consumed by acetogenic bacteria as their substrates. (iii) Methanogenic bacteria obtain energy by converting the acetate, carbon dioxide, and hydrogen into methane. The development of biofilms provides an appropriate environment for the development of the syntrophic association, an association of two or more metabolically different bacteria that are dependent on each other for the utilization of certain substrates for their energy purposes [19].
On the other hand, the EPS encasing the cells in a biofilm, which is composed of a complex mixture of proteins, lipids, extracellular-DNA (eDNA), and polysaccharides, not only assists in securing the adhesion of biofilm to the surface but also provide structural support, shield against host immune responses and antimicrobial agents and trap nutrients. In addition, it is also responsible for holding the community of cells in close proximity, enabling cell-to-cell communication (QS), and facilitating genetic material exchange via horizontal gene transfer [20].

6. Maturation and Architecture

These low-molecular-weight biochemicals are stimuli for bacteria to respond accordingly (inter or intra-species) and start cross-talk. Just stimuli are not environmental or not from the host, hence the name given to the autoinducer. This is based on their activity and how they act in their biological role. They stimulate the cells in the biofilm community by binding with the luxP proteins, which are periplasmic binding proteins (PBPs) or receptors, and induce gene expression. The bacterial cells continuously create these autoinducers, and as cell density rises, so does their production until a critical threshold concentration is reached [20,21]. Many target genes are either activated or repressed as a result of autoinducer receptor engagement. The coordination of virulence phenotypes and preservation of the ideal biofilm size are two benefits of this communication process for the entire microbial community [22]. Beyond population density controlling, quorum sensing also aids in the spreading of beneficial mutations in the biofilm colony, enhances access to nutrients, and contributes to antibiotic tolerance. In this stage, interstitial voids (channels) are also produced in the matrix that are filled with water and act as a circulatory system [23].
Among the genes that are regulated via quorum sensing, the bsmA and bsmB genes, as well as C4-HSL, control the maturity of the biofilm in a number of Gram-negative bacteria, including Serratia liquefaciens MG1. The bsmA and bsmB genes are important genes that encode proteins that facilitate bacterial aggregation and adhesion. In these bacteria, a mutation at one of the luxI or luxR (genes coding for signaling molecules or autoinducers) homologs causes a flaccid, architecturally undifferentiated biofilm to grow [18]. Figure 3 illustrates quorum sensing in the following manner.

7. Detachment/Dispersion of Biofilm

As the biofilm ages, it begins to accumulate harmful compounds and run out of resources. Thus, the cells begin to spread out to different areas in order to obtain nutrients, grow, and eliminate waste and situations that cause stress. Single cells or clusters of cells that slough off the biofilm disperse during this dispersion [1,24]. It is said that an oxygen or nutritional shortage triggers this preprogrammed mechanism. Fatty acid diffusible signal factor (DSF) (cis-11-methyl-2-dodecenoic acid) is stimulated by hunger, and this causes auto-phosphorylation, which in turn activates c-di-GMP phosphodiesterase, which breaks down c-di-GMP. When c-di-GMP degrades, planktonic cells are released, which dissolve part of the EPS, or shear forces tear clusters apart [1].
The production of various saccharolytic enzymes by the microbial communities within the biofilm facilitates the release of the microorganisms’ surface into a new area for colonization, which is another mechanism for the dissolution of EPS during the detachment process. For example, alginate lyase is produced by P. aeruginosa and Pseudomonas fluorescens, N-acetyl-heparosan lyase is produced by E. coli, and hyaluronidase is produced by Streptococcus equi for the lysis of the EPS matrix and subsequent detachment [19]. Following their release, these microorganisms either form new biofilms in other parts of the body or float freely on the surface by overexpressing the flagella protein, which aids in their movement [1,24]. Detachment of microbial cells and transfer to a new site aids in the spreading of infections [25].
In different bacterial species, individual cells inside a biofilm can separate from the biofilm. Bacteria can reproduce by spreading and/or aggregating, which enables them to colonies new surfaces and restart the formation of biofilms. In certain bacteria, QS control would govern the bacterial dispersion and/or detachment. Under conditions of overpopulation in nutrient-poor niches, QS can be a perfect way to mediate the release of bacteria from the biofilm so they can colonies other surfaces. Research has demonstrated that a mutation in the genes responsible for the dispersion of the affected bacteria primarily results in hyper-aggregation and/or an increase in the creation of the biofilm [18,26]. Quorum sensing is believed to be involved in regulating different steps of biofilm development, depending on the organisms and growth conditions (Figure 4).

8. Quorum Sensing and Cross-Communication in Bacteria

Bacteria secrete tiny chemicals (autoinducers, (AIs)) into their surroundings to enable cross-signaling. The name “quorum sensing” refers to this cross-talk in the microbial community [27,28]. Bacterial cell-to-cell communication enables the control of particular processes, including the formation of biofilms, the expression of virulence factors, the synthesis of secondary metabolites, and stress adaptation mechanisms like secretion systems (SS) and bacterial competition systems. These SS play a significant part in the communication between bacteria. Secretion systems are crucial to the biology of bacteria, where molecules are transferred, usually proteins, from the cytoplasm of bacteria to the outer membrane, from a donor bacterium to the environment, or to a recipient bacterium. It might also be the direct translocation of the molecules to the target host cell [29]. At large cell densities, quorum sensing controls the expression of genes. The concentration of an autoinducer, which the bacteria exude into the environment, reaches a threshold at high cell density and causes gene expression and the regulation of several cascades [30].
The milieu’s extracellular chemical signals that the bacteria make themselves have the ability to trigger bacterial quorum sensing signaling (Figure 3). Bacteria utilize QS signals, primarily composed of acyl-homoserine lactones (AHLs), autoinducing peptides (AIPs), and autoinducer-2 (AI-2), to participate in a range of physiological processes, such as motility, plasmid conjugation, biofilm formation, and antibiotic resistance. These mechanisms enable bacteria to adapt to and survive in adverse environments, and they also play a crucial role in regulating bacterial pathogenesis [31].
Different QS signals are used by Gram-positive and Gram-negative bacteria for cell-to-cell communication. Gram-negative bacteria are primarily responsible for producing AHL signaling molecules [32], while Gram-positive bacteria are responsible for producing AIP signaling molecules [33]. The AI-2 signals are produced and sensed by both Gram-positive and Gram-negative bacteria [34].
The two most crucial proteins needed for QS signaling are N-acyl-homoserine lactone (acyl-HSL) synthase (I protein) and a transcription factor known as an R protein that has acyl-HSL-dependent activity [35]. A positive feedback regulatory mechanism is established when the R protein–acyl–HSL complex stimulates transcription of the genes encoding the R and I proteins. The acyl-HSL molecule is hence referred to as an autoinducer (AI). Activated R proteins also cause the transcription of genes encoding virulence factors in pathogenic QS bacteria like P. aeruginosa [35,36]. LasR/I and RhlR/I QS proteins are organized in a signaling cascade in P. aeruginosa. The rhl regulon is activated by the LasR–AI complex and the RhlR–C4–HSL and LasR–3–oxo–C12–HSL complexes both activate genes that encode virulence factors and other proteins required for survival in a human host [36].
Biofilms, which are often mixed-species habitats present in many clinical, industrial, and natural settings, exhibit significant QS signal concentrations due to high cell densities. In multispecies biofilm communities, quorum sensing may exhibit both hostile and cooperative relationships [28].
Synergistic Interactions: It has been proposed that AI-2 QS is crucial for encouraging interspecies interactions in the oral cavity. In lung infections caused by cystic fibrosis, interspecies QS contacts among AHL-producing microorganisms are crucial [28].
Antagonistic Interactions: Microorganisms in the same niche are in constant competition with one another for shared resources. Mixed-species biofilms can have intense competition between competing species, with large numbers of cells attached in close proximity to one another. Two processes that may aid certain species in competing within biofilm communities are the synthesis of bacteriocin and pH reduction. QS has the ability to control the production of bacteriocin, which could be one of the ways that QS influences competition [28,37].

9. Communication in Gram-Negative and Gram-Positive Bacteria

The chemical signal molecules or autoinducers that quorum sensing bacteria create and release eventually regulate the gene expression of the entire bacterial population. Gram-positive and Gram-negative bacteria both have quorum sensing systems, which use various chemical cues to regulate distinct target genes [3].
N-acyl homoserine lactones (AHLs) are an autoinducer signal molecule produced by Gram-negative proteobacteria that facilitates intra-species communication. Homoserine lactone (HSL) rings, which carry acyl chains ranging in length from C4 to C18, are the building blocks of acyl homoserine lactones [38,39]. Since acyl homoserine lactone molecules are known to diffuse freely across cell membranes, it is presumed that they will have little trouble diffusing freely in the biofilm matrix to reach their target receptors [40]. One well-known use of QS is the control of gene expression by AHL.
Proteins involved in QS regulation are the I gene (luxI, phzI, traI, lasI, etc.), which converts cellular precursors into one or more AHL signals and AHL responsive regulatory protein (R protein), encoded by a gene referred to as an R gene (luxR, phzR, traR, lasR, etc.), required for the activation of specific genes. At low cell densities, the AHL signal either diffuses out of the cell following a concentration gradient or is actively transported out of the cell. As cell density increases, the concentration of AHL signal accumulates within the cell. On reaching a threshold level, the AHL interacts with the R protein, resulting in the dimerization of the R protein. This causes the R protein dimer to bind to a specific sequence in the promoter of the QS-regulated gene(s), which recruits RNA polymerase and activates gene expression [3,40].
The traditional AHL-mediated QS communication networks are absent from Gram-positive bacteria. The majority of Gram-positive bacteria use small peptides as their primary communication molecules. But, some use γ-butyrolactones (produced by Streptomyces species), molecules structurally related to AHLs, to regulate specific gene expression in a cell density-dependent manner. Gram-positive bacteria lack a porous outer membrane and instead contain a thick peptidoglycan layer that may restrict diffusion of the AHL signals via the cell wall [41].
Peptide signaling is used by Gram-positive bacteria, and autoinducing peptides (AIPs) are oligopeptides that serve as signal molecules. Gradually increasing cell density leads to a rise in the concentration of peptide autoinducers. When the peptide autoinducers connect to membrane-bound histidine kinase receptors (H), they trigger a series of auto-phosphorylation events that lead to the phosphorylation of a conserved histidine residue in the cytoplasmic side by adenosine triphosphate (ATP). As a result, the phosphate group moved to a response regulator’s aspartate residue (D). Target gene expression is regulated by these regulators, which function as transcription factors that bind DNA. Therefore, the transition from low cell density (LCD) to high cell density (HCD) is modulated by a positive feedback process that is akin to the LuxR/LuxI system [33].
Because tiny peptides are expected to interact with charged molecules, signaling peptides produced by Gram-positive bacteria are likely impacted by physical, chemical, and biological variables inside a biofilm [41]. The synthesis of a signal peptide in Gram-positive bacteria is significantly more costly. Gram-positive biofilms’ signal peptide-mediated QS and activities will be significantly influenced by nutrients or energy sources [42].
A two-component regulatory system is included in a QS variation used by the majority of Gram-positive bacteria. The term “three-component QS system” refers to this combination regulatory system. A cytoplasmic response regulator protein (RR) and a histidine kinase (HSK) sensor protein located in the cell membrane make up this three-component quorum sensing system. The generating cell secretes an autoinducing peptide (AIP), which is coupled to this two-component system [43]. Probiotics are a kind of microorganisms that are another example of Gram-positive cell–cell signaling. Probiotics are beneficial bacteria found in the intestines that improve the health of their human or animal hosts by preventing harmful bacteria from colonizing. Probiotics prevent colonization by producing peptides outside of cells called bacteriocins (antimicrobial molecules that are secreted while bacteria are in their biofilm state) [3].

10. Clinical Implication of Biofilms

According to the National Institutes of Health (NIH more than 80% of all microbial infections are biofilm-related [44]. These kinds of infections are hard to diagnose and treat.
Ear infections: There are a number of pathogens capable of causing either otitis externa or otitis media. Most otitis media infecting pathogens relate to infections of repertory infections. Biofilm formation aided the chance for Non-typeable Haemophilus influenzae (NTHi) Moraxella catarrhalis, Streptococcus pneumoniae, and Pseudomonas aeruginosa to cause different ear infections. For otitis externa, using hearing aids increased the chance of biofilm formation [45,46].
Eye infection: A corneal infection called bacterial keratitis can impair vision or even result in the loss of vision of the affected eye. In developing nations, it continues to be a leading cause of blindness. Common causal culprits include Staphylococcus aureus and Pseudomonas aeruginosa, both of which are known to form biofilm populations on the corneal surface [47,48].
Cystic fibrosis (CF): It is linked to P. aeruginosa, which produces oily mucus in the lungs that obstructs airways and makes breathing difficult for patients. The majority of P. aeruginosa infections acquired in hospitals are not always curable, while antibiotic therapy frequently reduces illness symptoms. P. aeruginosa biofilms, which serve as reservoirs for disease recurrence, are primarily to blame for the lack of a full cure [49]. The elements of biofilms, such as alginate, the main polysaccharide in the P. aeruginosa matrix, are virulence factors in addition to serving as disease reservoirs. Alginate, for instance, can harm the lungs [50].
Dental plaque: There are reportedly more than 700 different types of bacteria and archaea in tooth plaque. Many biofilms make up dental plaque. But, the makeup of disease-associated plaque biofilms differs greatly from that of the healthy plaque biofilm [51].
Dental biofilm is reformed as soon as the teeth are cleaned because of the pellicle’s adsorption, an organic coating that serves as a location for bacterial receptors. Bacteria stick to previously attached bacteria once pioneer bacteria make direct contact with the pellicle. The most frequent early colonizers of dental biofilms are streptococcal species. If the dental biofilm is not disturbed, it will shift from being primarily formed of Gram-positive cocci to a high number of cocci, filamentous organisms, spirils, and spirochetes [52].
Wounds: Chronic wounds frequently include biofilms. In contrast to an acute wound, which is typically unrelated to biofilm, a chronic wound caused by biofilm endures and heals slowly. Although P. aeruginosa biofilms are embedded in the deep layers of wounds, biofilms typically grow on the outer layer of wounds and are challenging to diagnose using a standard wound swab culture [53,54].
Urinary infection: Urinary tract biomaterials, like catheters, raise the risk of bacterial biofilm formation and subsequent urinary tract infection [54,55]. The artificial alien material offers surfaces on which bacteria can adhere. Bacterial biofilms infect nearly all urinary catheters. Patients may need to replace obstructed catheters due to the presence of biofilms such as P. mirabilis biofilms, which have the potential to be crystalline in nature and can obstruct catheters [56].
Prosthetic joint infection: Bacteria causing prosthetic joint infection are usually Gram-positive, such as staphylococci. Most often, immediately after surgery, bacteria (which could come from blood or lymph) attach to the surface of prosthetic joints to form biofilms (Table 1). Unlike typical bacterial infections that give symptoms like fever, it could take a while before symptoms of the biofilms on these implants, such as pain, emerge [57].
Cardiac valve infection: Endocarditis of the prosthetic valve is a condition caused by bacterial biofilm on the mechanical heart valve. S. epidermidis, S. aureus, Streptococcus species, Corynebacterium species, and Enterococcus species are the species that cause endocarditis. The artificial heart valve may become blocked or disrupted by accumulated biofilm, which could cause turbulence, reduced flow, or even leakage (Table 1). It is possible for detached biofilm cells to spread throughout the bloodstream and infect different organs. Blood at the terminal may become blocked by biofilm pieces in the blood circulation [58].
Table 1. Summary of biofilm-associated microorganisms commonly isolated from selected indwelling medical devices [54,59].
Table 1. Summary of biofilm-associated microorganisms commonly isolated from selected indwelling medical devices [54,59].
Indwelling Medical DeviceOrganisms
Central venous catheter [58,59]Coagulase-negative staphylococci, S. aureus, Enterococcus faecalis,
K. pneumoniae, P. aeruginosa
Prosthetic heart valve [54,59]Viridans Streptococcus, coagulase-negative staphylococci, enterococci, S. aureus
Urinary catheter [54,59]Staphylococcus epidermidis, Escherichia coli, Klebsiella pneumoniae, Enterococcus faecalis, Proteus mirabilis
Artificial hip prosthesis [54,59]Coagulase-negative staphylococci, b-hemolytic streptococci, enterococci, Proteus mirabilis, Bacterioides species, Staphylococcus aureus, viridans Streptococcus, E. coli, P. aeruginosa
Artificial voice prosthesis [54,59]Streptococcus mitis, Streptococcus salivarius, Rothia dentrocariosa, Streptococcus sobrinus, Staphylococcus epidermidis, Stomatococcus mucilaginous
Intrauterine device [54,59]S. epidermidis, Corynebacterium species, S. aureus, Micrococcus species, Lactobacillus plantarum, group B streptococci, Enterococcus species

11. Biofilms Enhance Antibiotic Tolerance and Resistance

The ability of bacteria to survive antibiotic therapy without being able to multiply is known as antibiotic tolerance, whereas the ability to multiply under the same circumstances is known as resistance [7]. According to studies, bacteria that develop in biofilms are frequently thousands of times more resistant to antibiotic treatment than their counterparts that grow in planktonic media. Biofilm-mediated antibiotic tolerance does not seem to be primarily caused by the well-understood antibiotic resistance mechanisms in planktonic bacteria [60], which include mutations, efflux pumps, and antibiotic-modifying enzymes. For example, naturally drug-susceptible bacterial strains frequently show high levels of antibiotic tolerance when living in biofilms; nevertheless, these cells rapidly regain their susceptibility to antibiotics when they are freed from the biofilm and reintegrated into the main community. Consequently, BAT is thought to involve alternative mechanisms to bacterial antimicrobial resistance [1].
Antibiotic resistance in biofilms can be either innate (arising from the formation of the biofilm) or induced (arising from the body’s reaction to antimicrobial therapy). Since most antibiotics target rapidly replicating bacterial cells, innate BAT mechanisms include limited penetration due to EPS, reduced growth rate due to oxygen and food deprivation, and persister cell presence [1]. Furthermore, the efficacy of antibiotics may be limited by the capacity of bacteria within biofilms to undertake anaerobic metabolism in the absence of oxygen. It has also been observed that the cation-chelating characteristics of eDNA, which is produced during autolysis in the EPS, neutralize the effects of antibiotics such as tobramycin. Certain bacteria, such as P. aeruginosa, can also gain resistance by horizontal gene transfer. Multidrug efflux pumps are sometimes used by bacteria to transfer antibiotic drugs from developing biofilms into the extracellular matrix, hence promoting resistance [7].

12. Quorum Sensing in Antibiotic Tolerance

Bacteria can interact with one another throughout the biofilm-building process thanks to QS. Planktonic cell metabolism is regulated by QS, which can also result in the formation of microbial biofilms and increased antibiotic resistance. Bacterial QS facilitates the biofilm form in which the bacterial cells hide themselves from antibiotics reaching them. In addition to this, QS alters the gene expression cascades at which the microbial metabolism and susceptibility to the existing antibiotics could be altered. The bacteria in biofilms also communicate via horizontal gene exchange, where the resistance genes could also be transferred [4,6]. In this regard, further investigations should be carried out. Most of the literature fails to conclude how QS and biofilm formation increase antibiotic resistance.

13. Detection of Biofilm and Quorum Sensing Signaling Molecules

There are several ways to find evidence of biofilm formation. These consist of the Fluorescence Microscopy Examination, Tissue Culture Plate, Tube technique (TM), Congo Red Agar method (CRA), bioluminescent test, and piezoelectric sensors [61,62]. Moreover, a number of sophisticated approaches, such as microscopy, spectroscopic, and immunological procedures, are available for the detection and investigation of biofilms at research facilities. These techniques, however, are not particularly appropriate for actual application in industry due to their complexity, high requirement for specialized personnel, and sophisticated instrumentation [62].
For the detection of AHL, radiolabeled assays, colorimetric assays, and biosensors are the most often used analytical techniques. AHL is identified and quantified using a variety of techniques, including gas chromatography–mass spectrometry (GC-MS), liquid chromatography–mass spectrometry (LC-MS), capillary electrophoresis–mass spectrometry (CE-MS), matrix-assisted laser desorption ionization–mass spectrometry (MALDI-MS), and nuclear magnetic resonance spectroscopy. However, GC-MS and high-performance liquid chromatography (HPLC) are two analytical methods that can be employed for the identification and quantification of other QS molecules [62,63,64].

14. Prevention, Control, and Removal of Biofilm

To date, three main approaches that focus on various phases of biofilm development have been investigated to regulate the production of biofilms. Preventing bacteria from adhering to surfaces in the first place is the first tactic. The third tactic is signal interference, which interferes with the bacterial communication system or the QS system. The second technique is to interrupt the biofilm maturation process (matrix degradation) [62].

15. Inhibition of Initial Attachment

As previously mentioned, a number of substances, such as adhesion surface proteins, pili or fimbriae, and exopolysaccharides, mediate the attachment of bacteria to surfaces [65]. Biofilm production is more likely on surfaces that are rough, hydrophobic, and covered in surface conditioning coatings. Thus, early cell attachment is prevented by altering the chemical or physical characteristics of indwelling medical device surfaces [66].
1.
Inhibition of initial attachment by Altering the Chemical Properties of materials
The most widely utilized chemical techniques for altering the surfaces of biomedical devices to stop biofilm formation include antibiotics, biocides, and ion coatings. It has been demonstrated that using antibiotic-impregnated catheters, such as those containing rifampin or minocycline, can reduce the risk of S. aureus bloodstream infections linked to biofilms in healthcare settings [67]. Furthermore, it is hypothesized that catheters impregnated with norfloxacin, nitrofurazone, and gentamicin may help reduce biofilm-associated UTIs [68].
It is also known that a number of antimicrobial peptides, including peptide 1018, prevent the formation of biofilms in many bacterial pathogens. In P. aeruginosa, E. coli, A. baumannii, K. pneumoniae, S. aureus, and Salmonella typhimurium, this peptide is thought to function as a biofilm inhibitor [69]. Furthermore, it has been observed that lantibiotics, a class of peptide antibiotics that includes nisin, subtilin, epidermin, and gallidermin, prevent S. aureus and S. epidermidis from forming biofilms [70].
Conversely, chelators that obstruct the role of metal ions in the production of biofilms are also regarded as biofilm inhibitors. Medical implants have long employed metallic silver, silver salts, and silver nanoparticles as antimicrobial agents to combat bacteria like Candida albicans, E. coli, S. aureus, P. aeruginosa, and Klebsiella species. It is anticipated that the application of silver therapy will impede DNA replication, ribosomal and cellular protein expression, and the respiration process, ultimately resulting in cell death [71]. Furthermore, in the presence of nanoparticles, medications, including amoxicillin, vancomycin, penicillin G, erythromycin, and clindamycin, showed enhanced antibacterial activity against S. aureus [72].
2.
Inhibition of initial attachment by Changing the Physical Properties of materials
The capacity of bacteria to adhere to surfaces is significantly influenced by the hydrophobicity and surface charge of implant materials. Therefore, it has been demonstrated that altering the hydrophobicity and surface charge of polymeric materials can effectively prevent the formation of biofilms. It has been observed that hydrophilic polymers, like hyaluronic acid and poly N-vinylpyrrolidone, inhibit S. epidermidis adhesion more than polyurethane catheters and silicone closures, respectively [56]. Furthermore, several hydrogel coatings with hydrophilic qualities have been created and have been shown to decrease bacterial adhesion, particularly for ureteral stents [73]. Because of their incredibly low wettability, superhydrophobic surfaces like titanium, fluorinated silica coating, and aerosol-aided chemical vapor deposition are suggested to decrease bacterial adherence and biofilm formation [74]. According to reports, heparin covering vascular catheters prevents thrombosis and microbial colonization, ultimately lowering the risk of catheter-related infections by interfering with the formation of bacterial biofilms by making the catheter negatively charged. Because surface roughness can change the hydrophobicity, which in turn affects bacterial adherence, it can also have an impact on biofilm development [75].

16. Biofilm Removal

Removing Biofilm by Matrix-Degrading Enzymes

The typical composition of the biofilm matrix is EPS-inclosing proteins, nucleic acids (eDNA and eRNA), lipids, polysaccharides, and other biomolecules. Via inhibiting the spread of antibiotics or directly causing antibiotic resistance, EPS and eDNAs play a significant role in antibiotic resistance. Dissociating the matrix, which makes up more than 90% of the dry mass of the biofilm, is a useful antibiofilm strategy because it exposes the sessile cells to antibiotics and the host immune system [76]. Enzymes that break down the biofilm matrix can be classified into three groups that break down polysaccharides: nucleases, proteases, and enzymes [77]. Actinobacillus actinomycetemcomitans produces Dispersin-B, a bacterial glycoside hydrolase that breaks down poly-N-acetylglucosamine (PNAG), a significant matrix extracellular polymer of E. coli and Staphylococcus species. Furthermore, triclosan and dispersin-B treatment successfully decreased the production of biofilms in S. aureus, S. epidermidis, and E. coli [78]. On the other hand, Endolysins, a class of peptidoglycan hydrolases produced by bacteriophages, are reported to digest the cell wall of bacteria, which in turn disrupts biofilms [79].
Deoxyribonuclease I’s ability to break down eDNA has been shown to spread biofilms in a variety of bacteria, including strains of Staphylococcus, A. baumannii, E. coli, H. influenzae, K. pneumoniae, and P. aeruginosa [80]. By using Proteinase K to efficiently cleave matrix proteins, biofilm dispersal may also be achievable. Staphylococcus biofilms were shown to be effectively eliminated by treatment with dispersin B, followed by proteinase K or trypsin [81].
Surfactants: Using surfactants such as sodium dodecyl sulfate (SDS), cetyltrimethylammonium bromide (CTAB), Tween 20, and Triton X-100 can help facilitate biofilm dispersal or detachment. Furthermore, it has been demonstrated that B. subtilis produces surfactin, a cyclic lipopeptide biosurfactant, which inhibits the formation of biofilms and promotes their dispersal in S. typhimurium, E. coli, and P. mirabilis [66].
Free Fatty Acids: Studies have demonstrated the antibiofilm activity of free fatty acids against a variety of harmful bacteria. According to a paper by Kumar, P. et al., 2020, P. aeruginosa’s cis-2-decenoic acid is an organic chemical that can disperse established biofilms made by E. coli, K. pneumoniae, P. mirabilis, S. pyogenes, B. subtilis, S. aureus, and C. albicans [82]. Xanthomonas campestris produces cis-11-methyl-2-decanoic acid, or DSF, which can also promote biofilm dispersal by regulating the synthesis of an enzyme that breaks down exopolysaccharides [83].
Nitric oxide donors: Nitric oxide generators such as sodium nitroprusside (SNP), S-nitrosoL-glutathione (GSNO), and S-nitroso-N-acetylpenicillamine (SNAP) that are reported to induce biofilm dispersal in P. aeruginosa [84]. A low dose of nitric oxide generators dispersed P. aeruginosa biofilms both in vitro and in cystic fibrosis sputum and enhanced the effect of antibiotics on biofilm-dispersed cells [66].

17. Biofilm Inhibition by Quorum Quenching (QQ)

Three QS system groups are recognized based on signaling molecules (autoinducers): Gram-negative bacteria based on N-acyl homoserine lactones (AHLs), Gram-positive bacteria based on autoinducing peptide (AIP), and both Gram-negative and Gram-positive bacteria based on autoinducer-2 (AI-2). It has been proposed that inhibiting cell–cell communication or quorum quenching (QQ) could be an intriguing method for stopping biofilm development because QS is essential to biofilm formation [85,86].
AHL signal synthase, which is produced by the LuxI gene, and AHL receptor protein, which is encoded by the LuxR gene, are important for the functionality of AHL. AHL-mediated phenotypes have been attenuated by QQ techniques, including inhibiting AHL synthesis, inhibiting signal transit, degrading signal molecules, inhibiting AHL receptor production, inhibiting the formation of AHL-receptor complexes, and so forth [66].

18. Inhibition of Signal Synthesis

Several reports have shown that mutations affecting signal molecule synthesis have an adverse effect on biofilm formation. For example, the P. aeruginosa strain that lacked 3-oxo-C12-HSL production has shown impaired biofilm formation [87]. Several other species with mutations in the gene encoding for AHL and AI-2 synthesis enzymes were not able to produce biofilms properly. Thus, blocking signal production has been considered an important strategy to control biofilm formation.
It is commonly recognized that molecules like S-adenosyl-homocysteine (SAH), sinefugin, 5-methylthioadenosine (MTA), and butyryl-SAM, which are analogs of the AHL precursor molecule S-adenosyl-methionine (SAM), prevent P. aeruginosa from forming biofilms. It has also been found that the antibiotic azithromycin and the SAM biosynthesis inhibitor cycloleucine prevent the synthesis of AHL. Furthermore, it has been demonstrated that a number of inhibitors of the major enzymes involved in AI-2 synthesis lessen the formation of biofilms. However, it has been found that the minerals nickel (Ni2+) and cadmium (Cd2+) suppress the expression of the genes that produce AHL, which in turn suppresses cell–cell signaling and, ultimately, the formation of biofilms in B. multivorans [88,89].

19. Degradation of QS Signals

Enzymes that break down QS signaling molecules are produced by a variety of prokaryotes and certain eukaryotes. Four enzymes can break down AHLs; acylases and lactonases hydrolyze the amide bond and HSL ring of AHL, respectively; reductases and oxidases alter AHL activity but do not break it down [90]; oxidoreductases specifically target AI-2 [91]. Several bacterial strains have been shown to exhibit inhibited biofilm development upon administration of these degrading QQ enzymes. The biofilm architecture is upset by QQ enzymes, which makes the cells more susceptible to antibiotics. Following lactonase treatment, P. aeruginosa showed this situation [92]. It has been shown that in K. oxytoca and K. indica, the oxidoreductases convert the signaling molecules AHL and AI-2 to hydroxy-derivatives that are QS-inactive [66,91].

20. Inhibition of Signal Transport

The synthesized signaling molecules need to be exported and released into the extracellular space to be sensed by other bacterial cells for effective cell-to-cell communication. The role of multidrug-resistant efflux pumps in signal traffic was reported in different species.
Thus, inhibition of the efflux pump could also be an important strategy to alter the QS signaling cascade, thereby preventing biofilm formation and virulence. Several studies have tried to show the link between the physiological function of efflux pumps and biofilm formation. Of these in E. coli and Klebsiella strains, the inhibition of the efflux pump activity using efflux pump inhibitors (EPIs) reduced biofilm formation [93].
Inactivation efflux pump activity either genetically or chemically resulted in impaired biofilm formation in S. enteric serovar typhimurium [94], P. aeruginosa, and S. aureus, in which copper nanoparticles work well as EPI and anti-biofilm agents [95]. In addition, in P. aeruginosa, silver nanoparticles were also reported to disrupt the MDR efflux pump [96].

21. Antagonizing the Signal Molecules

Using inductor antagonists is another method of interfering with QS. These antagonist molecules have two possible ways of binding to the receptor: either they attach non-competitively to the receptor and prevent the signal from entering the cell, or they bind competitively with inductors for the same binding site [94].
For instance, it has been observed that AHL analogs that substituted a cyclopentyl or cyclohexanone ring for the lactone ring negatively impacted Serratia marcescens and P. aeruginosa biofilm formation. AHL-based QS signaling has also been shown to be antagonistic by natural substances such as bergamottin from grapefruit juice, patulin, cyclic sulfur compounds from garlic, and penicillic acid from a range of fungi. Furthermore, it is known that phenolic substances like baicalin hydrate and epigallocatechin inhibit AHL QS, which in turn influences the production of biofilms. Conversely, it has been observed that AI-2 analogs, including ursolic acid, isobutyl-4,5-dihydroxy-2,3-pentanedione, and phenyl-DPD, prevent the formation of biofilms in P. aeruginosa and E. coli and eliminate those that have already formed. Furthermore, a number of AIP mimics include shortened AIP versions and naturally occurring probiotic bacteria [70].

22. Conclusions

Bacterial biofilms are evidently ubiquitous and hardy, and dealing with them is a problem. The stages of bacterial development on implants were described in this paper, along with a number of technologies that may be used to prevent or treat biofilms that cause infections. In vitro and in vivo bacteria typically exhibit distinct behaviors. Thus, a thorough investigation of the in vivo behavior of bacterial biofilms is necessary. Recurrence of infections after treatment is another big issue, and currently, their resistance to phagocytes and medicines is an urgent worry. To reduce the rates of morbidity and mortality linked to their use, an alternative to antibiotics and repeated procedures is needed. Both in vitro and in vivo models are now being used to study the technologies discussed in the review. With growing success in the development of effective therapies one can expect their introduction to the market in the near future.

Author Contributions

Conceptualization writing or original draft preparation, methodology, review, editing and validation M.E.; methodology, review, editing and validation; Z.A. and K.E. methodology, review, editing and validation B.G. methodology, supervision, review and validation T.K. and A.B. All authors have read and agreed to the published version of the manuscript.

Funding

This research received no external funding.

Conflicts of Interest

The authors declare that there were no competing interests.

Abbreviations

AHL: Acyl-Homoserine Lactones, AIs: Autoinducers, AI-2: Autoinducer-2, AIP: Autoinducing Peptides, BAT: Biofilm antibiotic tolerance, DNA: Deoxyribose Nucleic Acid, EPS: Extracellular polymeric substance, eDNA: Extracellular-DNA, HSL: Homoserinelactone, MDR: Multi-Drug Resistance, QS: Quorum sensing, QQ: Quorum quenching, SAM: S-adenosyl-methionine

References

  1. Costerton, J.W.; Stewart, P.S.; Greenberg, E.P. Bacterial biofilms: A common cause of persistent infections. Science 1999, 284, 1318–1322. [Google Scholar] [CrossRef] [PubMed]
  2. Carette, J.; Nachtergael, A.; Duez, P.; El Jaziri, M.; Rasamiravaka, T. Natural compounds inhibiting Pseudomonas aeruginosa biofilm formation by targeting quorum sensing circuitry. In Bacterial Biofilms; IntechOpen: Rijeka, Croatia, 2020. [Google Scholar]
  3. Zea, L.; McLean, R.J.; Rook, T.A.; Angle, G.; Carter, D.L.; Delegard, A.; Denvir, A.; Gerlach, R.; Gorti, S.; McIlwaine, D.; et al. Potential biofilm control strategies for extended spaceflight missions. Biofilm 2020, 2, 100026. [Google Scholar] [CrossRef] [PubMed]
  4. Mendes, S.G.; Combo, S.I.; Allain, T.; Domingues, S.; Buret, A.G.; Da Silva, G.J. Co-regulation of biofilm formation and antimicrobial resistance in Acinetobacter baumannii: From mechanisms to therapeutic strategies. Eur. J. Clin. Microbiol. Infect. Dis. 2023, 42, 1405–1423. [Google Scholar] [CrossRef] [PubMed]
  5. Silva, E.; Teixeira, J.A.; Pereira, M.O.; Rocha, C.M.; Sousa, A.M. Evolving biofilm inhibition and eradication in clinical settings through plant-based antibiofilm agents. Phytomedicine 2023, 119, 154973. [Google Scholar] [CrossRef] [PubMed]
  6. Satpathy, S.; Sen, S.K.; Pattanaik, S.; Raut, S. Review on bacterial biofilm: An universal cause of contamination. Biocatal. Agric. Biotechnol. 2016, 7, 56–66. [Google Scholar] [CrossRef]
  7. Verderosa, A.D.; Totsika, M.; Fairfull-Smith, K.E. Bacterial biofilm eradication agents: A current review. Front. Chem. 2019, 7, 824. [Google Scholar] [CrossRef]
  8. Khatoon, Z.; McTiernan, C.D.; Suuronen, E.J.; Mah, T.-F.; Alarcon, E.I. Bacterial biofilm formation on implantable devices and approaches to its treatment and prevention. Heliyon 2018, 4, e01067. [Google Scholar] [CrossRef] [PubMed]
  9. Percival, S.L.; McCarty, S.M.; Lipsky, B. Biofilms and wounds: An overview of the evidence. Adv. Wound Care 2015, 4, 373–381. [Google Scholar] [CrossRef] [PubMed]
  10. Øilo, M.; Bakken, V. Biofilm and Dental Biomaterials. Materials 2015, 8, 2887–2900. [Google Scholar] [CrossRef]
  11. Singh, S.; Singh, S.K.; Chowdhury, I.; Singh, R. Understanding the mechanism of bacterial biofilms resistance to antimicrobial agents. Open Microbiol. J. 2017, 11, 53. [Google Scholar] [CrossRef] [PubMed]
  12. Ha, D.-G.; O’Toole, G.A. c-di-GMP and its Effects on Biofilm Formation and Dispersion: A Pseudomonas aeruginosa Review. Microbiol. Spectr. 2015, 3, 27. [Google Scholar] [CrossRef] [PubMed]
  13. Stabnikova, O.; Stabnikov, V.; Marinin, A.; Klavins, M.; Klavins, L.; Vaseashta, A. Microbial life on the surface of microplastics in natural waters. Appl. Sci. 2021, 11, 11692. [Google Scholar] [CrossRef]
  14. Achinas, S.; Charalampogiannis, N.; Euverink, G.J.W. A brief recap of microbial adhesion and biofilms. Appl. Sci. 2019, 9, 2801. [Google Scholar] [CrossRef]
  15. Ferriol-González, C.; Domingo-Calap, P. Phages for biofilm removal. Antibiotics 2020, 9, 268. [Google Scholar] [CrossRef] [PubMed]
  16. Tribedi, P.; Sil, A. Cell surface hydrophobicity: A key component in the degradation of polyethylene succinate by Pseudomonas sp. AKS 2. J. Appl. Microbiol. 2014, 116, 295–303. [Google Scholar] [CrossRef] [PubMed]
  17. Jamal, M.; Ahmad, W.; Andleeb, S.; Jalil, F.; Imran, M.; Nawaz, M.A.; Hussain, T.; Ali, M.; Rafiq, M.; Kamil, M.A. Bacterial biofilm and associated infections. J. Chin. Med. Assoc. 2018, 81, 7–11. [Google Scholar] [CrossRef] [PubMed]
  18. Hadla, M.; Halabi, M.A. Effect of quorum sensing. In Comprehensive Analytical Chemistry; Elsevier: Amsterdam, The Netherlands, 2018; pp. 95–116. [Google Scholar]
  19. Dang, H.; Lovell, C.R. Microbial surface colonization and biofilm development in marine environments. Microbiol. Mol. Biol. Rev. 2016, 80, 91–138. [Google Scholar] [CrossRef]
  20. Campoccia, D.; Montanaro, L.; Arciola, C.R. Extracellular DNA (eDNA). A major ubiquitous element of the bacterial biofilm architecture. Int. J. Mol. Sci. 2021, 22, 9100. [Google Scholar] [CrossRef] [PubMed]
  21. Abisado, R.G.; Benomar, S.; Klaus, J.R.; Dandekar, A.A.; Chandler, J.R. Bacterial quorum sensing and microbial community interactions. MBio 2018, 9, e02331-17. [Google Scholar] [CrossRef]
  22. Mangwani, N.; Kumari, S.; Das, S. Bacterial biofilms and quorum sensing: Fidelity in bioremediation technology. Biotechnol. Genet. Eng. Rev. 2016, 32, 43–73. [Google Scholar] [CrossRef] [PubMed]
  23. Jakubovics, N.S.; Burgess, J.G. Extracellular DNA in oral microbial biofilms. Microbes Infect. 2015, 17, 531–537. [Google Scholar] [CrossRef] [PubMed]
  24. Gupta, P.; Sarkar, S.; Das, B.; Bhattacharjee, S.; Tribedi, P. Biofilm, pathogenesis and prevention—A journey to break the wall: A review. Arch. Microbiol. 2016, 198, 1–15. [Google Scholar] [CrossRef] [PubMed]
  25. Abebe, G.M. The role of bacterial biofilm in antibiotic resistance and food contamination. Int. J. Microbiol. 2020, 2020, 1705814. [Google Scholar] [CrossRef] [PubMed]
  26. Xavier, J.B. Sociomicrobiology and pathogenic bacteria. Microbiol. Spectr. 2016, 4, 12. [Google Scholar] [CrossRef] [PubMed]
  27. Zhao, Y.-L.; Zhou, Y.-H.; Chen, J.-Q.; Huang, Q.-Y.; Han, Q.; Liu, B.; Cheng, G.-D.; Li, Y.-H. Quantitative proteomic analysis of sub-MIC erythromycin inhibiting biofilm formation of S. suis in vitro. J. Proteom. 2015, 116, 1–14. [Google Scholar] [CrossRef]
  28. Steinberg, D. Dental Chatter: Bacterial Cross-Talk in the Biofilm of the Oral Cavity. Isr. J. Chem. 2015, 56, 273–281. [Google Scholar] [CrossRef]
  29. Pena, R.T.; Blasco, L.; Ambroa, A.; González-Pedrajo, B.; Fernández-García, L.; López, M.; Bleriot, I.; Bou, G.; García-Contreras, R.; Wood, T.K.; et al. Relationship between quorum sensing and secretion systems. Front. Microbiol. 2019, 10, 1100. [Google Scholar] [CrossRef] [PubMed]
  30. Rabin, N.; Zheng, Y.; Opoku-Temeng, C.; Du, Y.; Bonsu, E.; Sintim, H.O. Biofilm formation mechanisms and targets for developing antibiofilm agents. Future Med. Chem. 2015, 7, 493–512. [Google Scholar] [CrossRef] [PubMed]
  31. Eickhoff, M.J.; Bassler, B.L. SnapShot: Bacterial quorum sensing. Cell 2018, 174, 1328.e1. [Google Scholar] [CrossRef] [PubMed]
  32. Mellbye, B.L.; Spieck, E.; Bottomley, P.J.; Sayavedra-Soto, L.A. Acyl-homoserine lactone production in nitrifying bacteria of the genera Nitrosospira, Nitrobacter, and Nitrospira identified via a survey of putative quorum-sensing genes. Appl. Environ. Microbiol. 2017, 83, e01540-17. [Google Scholar] [CrossRef] [PubMed]
  33. Bhatt, V.S. Quorum sensing mechanisms in gram positive bacteria. In Implication of Quorum Sensing System in Biofilm Formation and Virulence; Springer: Berlin/Heidelberg, Germany, 2018; pp. 297–311. [Google Scholar]
  34. Gu, Y.; Tian, J.; Zhang, Y.; Wu, R.; Li, L.; Zhang, B.; He, Y. Dissecting signal molecule AI-2 mediated biofilm formation and environmental tolerance in Lactobacillus plantarum. J. Biosci. Bioeng. 2021, 131, 153–160. [Google Scholar] [CrossRef] [PubMed]
  35. Zhao, X.; Yu, Z.; Ding, T. Quorum-sensing regulation of antimicrobial resistance in bacteria. Microorganisms 2020, 8, 425. [Google Scholar] [CrossRef] [PubMed]
  36. Khan, F.; Javaid, A.; Kim, Y.-M. Functional diversity of quorum sensing receptors in pathogenic bacteria: Interspecies, intraspecies and interkingdom level. Curr. Drug Targets 2019, 20, 655–667. [Google Scholar] [CrossRef] [PubMed]
  37. Kareb, O.; Aïder, M. Quorum sensing circuits in the communicating mechanisms of bacteria and its implication in the biosynthesis of bacteriocins by lactic acid bacteria: A review. Probiotics Antimicrob. Proteins 2020, 12, 5–17. [Google Scholar] [CrossRef] [PubMed]
  38. Buchan, A.; Mitchell, A.; Cude, W.N.; Campagna, S. Acyl-homoserine lactone-based quorum sensing in members of the marine bacterial Roseobacter clade: Complex cell-to-cell communication controls multiple physiologies. In Stress and Environmental Regulation of Gene Expression and Adaptation in Bacteria; Wiley Blackwell: Hoboken, NJ, USA, 2016; Volume 1, pp. 225–233. [Google Scholar]
  39. Mukherjee, S.; Bassler, B.L. Bacterial quorum sensing in complex and dynamically changing environments. Nat. Rev. Microbiol. 2019, 17, 371–382. [Google Scholar] [CrossRef] [PubMed]
  40. Athulya, K.S.; Chaturvedi, S. Approach to Quorum Sensing and Functions of Signal Molecules in Biofilms. Int. J. Pharma Res. Health Sci. 2020, 8, 3192–3194. [Google Scholar] [CrossRef]
  41. Haque, S.; Yadav, D.K.; Bisht, S.C.; Yadav, N.; Singh, V.; Dubey, K.K.; Jawed, A.; Wahid, M.; Dar, S.A. Quorum sensing pathways in Gram-positive and-negative bacteria: Potential of their interruption in abating drug resistance. J. Chemother. 2019, 31, 161–187. [Google Scholar] [CrossRef] [PubMed]
  42. D’Souza, G.; Shitut, S.; Preussger, D.; Yousif, G.; Waschina, S.; Kost, C. Ecology and evolution of metabolic cross-feeding interactions in bacteria. Nat. Prod. Rep. 2018, 35, 455–488. [Google Scholar] [CrossRef] [PubMed]
  43. Monnet, V.; Juillard, V.; Gardan, R. Peptide conversations in Gram-positive bacteria. Crit. Rev. Microbiol. 2016, 42, 339–351. [Google Scholar] [CrossRef] [PubMed]
  44. Mirzaei, R.; Mohammadzadeh, R.; Alikhani, M.Y.; Moghadam, M.S.; Karampoor, S.; Kazemi, S.; Barfipoursalar, A.; Yousefimashouf, R. The biofilm-associated bacterial infections unrelated to indwelling devices. IUBMB Life 2020, 72, 1271–1285. [Google Scholar] [CrossRef] [PubMed]
  45. Weeks, J.R.; Staples, K.J.; Spalluto, C.M.; Watson, A.; Wilkinson, T.M.A. The Role of Non-Typeable Haemophilus influenzae Biofilms in Chronic Obstructive Pulmonary Disease. Front. Cell Infect. Microbiol. 2021, 11, 720742. [Google Scholar] [CrossRef] [PubMed]
  46. Brescia, G.; Frosolini, A.; Franz, L.; Daloiso, A.; Fantin, F.; Lovato, A.; de Filippis, C.; Marioni, G. Chronic Otitis Media in Patients with Chronic Rhinosinusitis: A Systematic Review. Medicina 2023, 59, 123. [Google Scholar] [CrossRef] [PubMed]
  47. Urwin, L.; Okurowska, K.; Crowther, G.; Roy, S.; Garg, P.; Karunakaran, E.; MacNeil, S.; Partridge, L.J.; Green, L.R.; Monk, P.N. Corneal Infection Models: Tools to Investigate the Role of Biofilms in Bacterial Keratitis. Cells 2020, 9, 2450. [Google Scholar] [CrossRef] [PubMed]
  48. Agarwal, S.; Khan, T.A.; Vanathi, M.; Srinivasan, B.; Iyer, G.; Tandon, R. Update on diagnosis and management of refractory corneal infections. Indian J. Ophthalmol. 2022, 70, 1475–1490. [Google Scholar] [PubMed]
  49. Mangiaterra, G.; Amiri, M.; Cedraro, N.; Biavasco, F. Pseudomonas aeruginosa Biofilm Lung Infection in Cystic Fibrosis: The Challenge of Persisters. In Pseudomonas aeruginosa-Biofilm Formation, Infections and Treatments; IntechOpen: Rijeka, Croatia, 2021. [Google Scholar]
  50. Al-Wrafy, F.; Brzozowska, E.; Górska, S.; Gamian, A. Pathogenic factors of Pseudomonas aeruginosa-the role of biofilm in pathogenicity and as a target for phage therapy. Adv. Hyg. Exp. Med./Postep. Hig. Med. Dosw. 2017, 71, 78–91. [Google Scholar] [CrossRef] [PubMed]
  51. Larsen, T.; Fiehn, N.E. Dental biofilm infections–an update. APMIS 2017, 125, 376–384. [Google Scholar] [CrossRef] [PubMed]
  52. Takenaka, S.; Ohsumi, T.; Noiri, Y. Evidence-based strategy for dental biofilms: Current evidence of mouthwashes on dental biofilm and gingivitis. Jpn. Dent. Sci. Rev. 2018, 55, 33–40. [Google Scholar] [CrossRef] [PubMed]
  53. Hall, M.R.; McGillicuddy, E.; Kaplan, L.J. Biofilm: Basic principles, pathophysiology, and implications for clinicians. Surg. Infect. 2014, 15, 1–7. [Google Scholar] [CrossRef] [PubMed]
  54. Rajaramon, S.; Shanmugam, K.; Dandela, R.; Solomon, A.P. Emerging evidence-based innovative approaches to control catheter-associated urinary tract infection: A review. Front. Cell Infect. Microbiol. 2023, 13, 1134433. [Google Scholar] [CrossRef] [PubMed]
  55. Aitsev, A.A.; Vasilyev, A.V.; Shiryaev, A.S.; Kim, Y.K.; Arefieva, O.A.; Govorov, A.G.; Pushkar, D.P.; Spasokukotsky, M.C.C.H.N.S. Biofilm control in urological practice. Urologiia 2022, 1_2022, 81–88. [Google Scholar]
  56. Yuan, F.; Huang, Z.; Yang, T.; Wang, G.; Li, P.; Yang, B.; Li, J. Pathogenesis of Proteus mirabilis in catheter-associated urinary tract infections. Urol. Int. 2021, 105, 354–361. [Google Scholar] [CrossRef] [PubMed]
  57. Ahmed, S.S.; Begum, F.; Kayani, B.; Haddad, F.S. Risk factors, diagnosis and management of prosthetic joint infection after total hip arthroplasty. Expert Rev. Med. Devices 2019, 16, 1063–1070. [Google Scholar] [CrossRef] [PubMed]
  58. Xu, Y.; Larsen, L.H.; Lorenzen, J.; Hall-Stoodley, L.; Kikhney, J.; Moter, A.; Thomsen, T.R. Microbiological diagnosis of device-related biofilm infections. APMIS 2017, 125, 289–303. [Google Scholar] [CrossRef] [PubMed]
  59. Stoica, P.; Chifiriuc, M.; Rapa, M.; Lazăr, V. Overview of biofilm-related problems in medical devices. In Biofilms and Implantable Medical Devices; Elsevier: Amsterdam, The Netherlands, 2017; pp. 3–23. [Google Scholar]
  60. Tomar, A.; Broor, S.; Kaushik, S.; Bharara, T.; Arya, D. Synergistic effect of naringenin with conventional antibiotics against methicillin resistant Staphylococcus aureus. Eur. J. Mol. Clin. Med. 2021, 7, 2020. [Google Scholar]
  61. Mishra, S.K.; Basukala, P.; Basukala, O.; Parajuli, K.; Pokhrel, B.M.; Rijal, B.P. Detection of biofilm production and antibiotic resistance pattern in clinical isolates from indwelling medical devices. Curr. Microbiol. 2014, 70, 128–134. [Google Scholar] [CrossRef] [PubMed]
  62. Bhardwaj, A. A Comparative Appraisal of Detection of Biofilm Production Caused by Uropathogenic Escherichia coli in Tropical Catheterized Patients by Three Different Methods. Asian J. Pharm. (AJP) 2018, 12. [Google Scholar] [CrossRef]
  63. Torres, M.; Dessaux, Y.; Llamas, I. Saline environments as a source of potential quorum sensing disruptors to control bacterial infections: A review. Mar. Drugs 2019, 17, 191. [Google Scholar] [CrossRef] [PubMed]
  64. van Hoogstraten, S.; Kuik, C.; Arts, J.; Cillero-Pastor, B. Molecular imaging of bacterial biofilms—A systematic review. Crit. Rev. Microbiol. 2023, 1–22. [Google Scholar] [CrossRef] [PubMed]
  65. Berne, C.; Ellison, C.K.; Ducret, A.; Brun, Y.V. Bacterial adhesion at the single-cell level. Nat. Rev. Microbiol. 2018, 16, 616–627. [Google Scholar] [CrossRef] [PubMed]
  66. Subhadra, B.; Kim, D.H.; Woo, K.; Surendran, S.; Choi, C.H. Control of biofilm formation in healthcare: Recent advances exploiting quorum-sensing interference strategies and multidrug efflux pump inhibitors. Materials 2018, 11, 1676. [Google Scholar] [CrossRef] [PubMed]
  67. Bonne, S.; Mazuski, J.E.; Sona, C.; Schallom, M.; Boyle, W.; Buchman, T.G.; Bochicchio, G.V.; Coopersmith, C.M.; Schuerer, D.J. Effectiveness of minocycline and rifampin vs chlorhexidine and silver sulfadiazine-impregnated central venous catheters in preventing central line-associated bloodstream infection in a high-volume academic intensive care unit: A before and after trial. J. Am. Coll. Surg. 2015, 221, 739–747. [Google Scholar] [CrossRef] [PubMed]
  68. Delcaru, C.; Alexandru, I.; Podgoreanu, P.; Grosu, M.; Stavropoulos, E.; Chifiriuc, M.C.; Lazar, V. Microbial biofilms in urinary tract infections and prostatitis: Etiology, pathogenicity, and combating strategies. Pathogens 2016, 5, 65. [Google Scholar] [CrossRef] [PubMed]
  69. de la Fuente-Núñez, C.; Reffuveille, F.; Haney, E.F.; Straus, S.K.; Hancock, R.E. Broad-spectrum anti-biofilm peptide that targets a cellular stress response. PLoS Pathog. 2014, 10, e1004152. [Google Scholar] [CrossRef] [PubMed]
  70. Götz, F.; Perconti, S.; Popella, P.; Werner, R.; Schlag, M. Epidermin and gallidermin: Staphylococcal lantibiotics. Int. J. Med. Microbiol. 2014, 304, 63–71. [Google Scholar] [CrossRef] [PubMed]
  71. Besinis, A.; Hadi, S.D.; Le, H.; Tredwin, C.; Handy, R. Antibacterial activity and biofilm inhibition by surface modified titanium alloy medical implants following application of silver, titanium dioxide and hydroxyapatite nanocoatings. Nanotoxicology 2017, 11, 327–338. [Google Scholar] [CrossRef] [PubMed]
  72. Gandhi, H.; Khan, S. Biological Synthesis of Silver Nanoparticles and Its Antibacterial Activity. J. Nanomed. Nanotechnol. 2016, 7, 1000366. [Google Scholar] [CrossRef]
  73. Zumstein, V.; Betschart, P.; Albrich, W.C.; Buhmann, M.T.; Ren, Q.; Schmid, H.P.; Abt, D. Biofilm formation on ureteral stents-Incidence, clinical impact, and prevention. Swiss Med. Wkly. 2017, 147, w14408. [Google Scholar] [CrossRef] [PubMed]
  74. Wang, D.; Zhou, E.; Xu, D.; Lovley, D.R. Burning question: Are there sustainable strategies to prevent microbial metal corrosion? Microb. Biotechnol. 2023, 16, 2026–2035. [Google Scholar] [CrossRef]
  75. Schirmeister, C.G.; Hees, T.; Licht, E.H.; Mülhaupt, R. 3D printing of high density polyethylene by fused filament fabrication. Addit. Manuf. 2019, 28, 152–159. [Google Scholar] [CrossRef]
  76. Thorn, C.R.; Raju, D.; Lacdao, I.; Gilbert, S.; Sivarajah, P.; Howell, P.L.; Prestidge, C.A.; Thomas, N. Protective Liquid Crystal Nanoparticles for Targeted Delivery of PslG: A Biofilm Dispersing Enzyme. ACS Infect. Dis. 2021, 7, 2102–2115. [Google Scholar] [CrossRef]
  77. Li, X.-H.; Lee, J.-H. Antibiofilm agents: A new perspective for antimicrobial strategy. J. Microbiol. 2017, 55, 753–766. [Google Scholar] [CrossRef] [PubMed]
  78. Gawande, P.V.; Clinton, A.P.; LoVetri, K.; Yakandawala, N.; Rumbaugh, K.P.; Madhyastha, S. Antibiofilm efficacy of DispersinB® wound spray used in combination with a silver wound dressing. Microbiol. Insights 2014, 7, 9–13. [Google Scholar] [CrossRef] [PubMed]
  79. Chan, B.K.; Abedon, S.T. Bacteriophages and their enzymes in biofilm control. Curr. Pharm. Des. 2015, 21, 85–99. [Google Scholar] [CrossRef] [PubMed]
  80. Schulze, A.; Mitterer, F.; Pombo, J.P.; Schild, S. Biofilms by bacterial human pathogens: Clinical relevance-development, composition and regulation-therapeutical strategies. Microb. Cell 2021, 8, 28. [Google Scholar] [CrossRef] [PubMed]
  81. Wolfmeier, H.; Pletzer, D.; Mansour, S.C.; Hancock, R.E. New perspectives in biofilm eradication. ACS Infect. Dis. 2018, 4, 93–106. [Google Scholar] [CrossRef] [PubMed]
  82. Kumar, P.; Lee, J.-H.; Beyenal, H.; Lee, J. Fatty acids as antibiofilm and antivirulence agents. Trends Microbiol. 2020, 28, 753–768. [Google Scholar] [CrossRef] [PubMed]
  83. Deng, Y.; Lim, A.; Lee, J.; Chen, S.; An, S.; Dong, Y.-H.; Zhang, L.-H. Diffusible signal factor (DSF) quorum sensing signal and structurally related molecules enhance the antimicrobial efficacy of antibiotics against some bacterial pathogens. BMC Microbiol. 2014, 14, 51. [Google Scholar] [CrossRef] [PubMed]
  84. Cutruzzolà, F.; Frankenberg-Dinkel, N. Origin and impact of nitric oxide in Pseudomonas aeruginosa biofilms. J. Bacteriol. 2016, 198, 55–65. [Google Scholar] [CrossRef] [PubMed]
  85. Brackman, G.; Coenye, T. Quorum sensing inhibitors as anti-biofilm agents. Curr. Pharm. Des. 2015, 21, 5–11. [Google Scholar] [CrossRef] [PubMed]
  86. Sánchez-Jiménez, A.; Llamas, M.A.; Marcos-Torres, F.J. Transcriptional Regulators Controlling Virulence in Pseudomonas aeruginosa. Int. J. Mol. Sci. 2023, 24, 11895. [Google Scholar] [CrossRef] [PubMed]
  87. De Smet, J.; Wagemans, J.; Hendrix, H.; Staes, I.; Visnapuu, A.; Horemans, B.; Aertsen, A.; Lavigne, R. Bacteriophage-mediated interference of the c-di-GMP signalling pathway in Pseudomonas aeruginosa. Microb. Biotechnol. 2021, 14, 967–978. [Google Scholar] [CrossRef] [PubMed]
  88. Vega, L.M.; Mathieu, J.; Yang, Y.; Pyle, B.H.; McLean, R.J.; Alvarez, P.J. Nickel and cadmium ions inhibit quorum sensing and biofilm formation without affecting viability in Burkholderia multivorans. Int. Biodeterior. Biodegrad. 2014, 91, 82–87. [Google Scholar] [CrossRef]
  89. Kalia, V.C.; Patel, S.K.; Lee, J.-K. Bacterial biofilm inhibitors: An overview. Ecotoxicol. Environ. Saf. 2023, 264, 115389. [Google Scholar] [CrossRef] [PubMed]
  90. Paluch, E.; Rewak-Soroczyńska, J.; Jędrusik, I.; Mazurkiewicz, E.; Jermakow, K. Prevention of biofilm formation by quorum quenching. Appl. Microbiol. Biotechnol. 2020, 104, 1871–1881. [Google Scholar] [CrossRef] [PubMed]
  91. Weiland-Bräuer, N.; Kisch, M.J.; Pinnow, N.; Liese, A.; Schmitz, R.A. Highly effective inhibition of biofilm formation by the first metagenome-derived AI-2 quenching enzyme. Front. Microbiol. 2016, 7, 1098. [Google Scholar] [CrossRef] [PubMed]
  92. Kusada, H.; Tamaki, H.; Kamagata, Y.; Hanada, S.; Kimura, N. A novel quorum-quenching N-acylhomoserine lactone acylase from Acidovorax sp. strain MR-S7 mediates antibiotic resistance. Appl. Environ. Microbiol. 2017, 83, e00080-17. [Google Scholar] [CrossRef]
  93. Reza, A.; Sutton, J.M.; Rahman, K.M. Effectiveness of efflux pump inhibitors as biofilm disruptors and resistance breakers in gram-negative (ESKAPEE) bacteria. Antibiotics 2019, 8, 229. [Google Scholar] [CrossRef] [PubMed]
  94. Baugh, S.; Phillips, C.R.; Ekanayaka, A.S.; Piddock, L.J.; Webber, M.A. Inhibition of multidrug efflux as a strategy to prevent biofilm formation. J. Antimicrob. Chemother. 2014, 69, 673–681. [Google Scholar] [CrossRef]
  95. Christena, L.R.; Mangalagowri, V.; Pradheeba, P.; Ahmed, K.B.A.; Shalini, B.I.S.; Vidyalakshmi, M.; Anbazhagan, V.; Subramanian, N.S. Copper nanoparticles as an efflux pump inhibitor to tackle drug resistant bacteria. RSC Adv. 2015, 5, 12899–12909. [Google Scholar] [CrossRef]
  96. Browning, L.M.; Lee, K.J.; Cherukuri, P.K.; Nallathamby, P.D.; Warren, S.; Jault, J.-M.; Xu, X.-H.N. Single nanoparticle plasmonic spectroscopy for study of the efflux function of multidrug ABC membrane transporters of single live cells. RSC Adv. 2016, 6, 36794–36802. [Google Scholar] [CrossRef] [PubMed]
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Figure 1. PRISMA document selection from the database based on the criteria for qualitative analysis of this review.
Figure 1. PRISMA document selection from the database based on the criteria for qualitative analysis of this review.
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Figure 2. Diagrammatic depiction of the production of biofilms in bacteria. 1. Planktonic microbiological cells attach themselves to a surface for the initial attachment, which is a reversible attachment followed by irreversible attachment. 2. The cells divide and begin synthesizing an extracellular matrix of polymeric molecules. 3. As the microbial population expands, it becomes more densely packed and triggers activities that rely on signaling and QS. 4. The division of labor and the growth of specialized cells are first regulated by QS. Extracellular enzymes and water channels found in the biofilm matrix make it easier for nutrients to enter and remove waste. 5. Biofilm disruption or separation activation [15].
Figure 2. Diagrammatic depiction of the production of biofilms in bacteria. 1. Planktonic microbiological cells attach themselves to a surface for the initial attachment, which is a reversible attachment followed by irreversible attachment. 2. The cells divide and begin synthesizing an extracellular matrix of polymeric molecules. 3. As the microbial population expands, it becomes more densely packed and triggers activities that rely on signaling and QS. 4. The division of labor and the growth of specialized cells are first regulated by QS. Extracellular enzymes and water channels found in the biofilm matrix make it easier for nutrients to enter and remove waste. 5. Biofilm disruption or separation activation [15].
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Figure 3. Quorum sensing illustration: Two predominant chemicals (N-acylhomoserine lactones and furanosylborate diester) are important types of small-molecule autoinducers involved in quorum sensing. The relative proportion of autoinducers increases as cells transition from planktonic form to a densely populated mode [7].
Figure 3. Quorum sensing illustration: Two predominant chemicals (N-acylhomoserine lactones and furanosylborate diester) are important types of small-molecule autoinducers involved in quorum sensing. The relative proportion of autoinducers increases as cells transition from planktonic form to a densely populated mode [7].
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Figure 4. Quorum sensing molecular cascades (created at BioRender.com). Note: RP (regulator proteins), PBPS (periplasmic binding proteins).
Figure 4. Quorum sensing molecular cascades (created at BioRender.com). Note: RP (regulator proteins), PBPS (periplasmic binding proteins).
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Erkihun, M.; Asmare, Z.; Endalamew, K.; Getie, B.; Kiros, T.; Berhan, A. Medical Scope of Biofilm and Quorum Sensing during Biofilm Formation: Systematic Review. Bacteria 2024, 3, 118-135. https://doi.org/10.3390/bacteria3030008

AMA Style

Erkihun M, Asmare Z, Endalamew K, Getie B, Kiros T, Berhan A. Medical Scope of Biofilm and Quorum Sensing during Biofilm Formation: Systematic Review. Bacteria. 2024; 3(3):118-135. https://doi.org/10.3390/bacteria3030008

Chicago/Turabian Style

Erkihun, Mulat, Zelalem Asmare, Kirubel Endalamew, Birhanu Getie, Teklehaimanot Kiros, and Ayenew Berhan. 2024. "Medical Scope of Biofilm and Quorum Sensing during Biofilm Formation: Systematic Review" Bacteria 3, no. 3: 118-135. https://doi.org/10.3390/bacteria3030008

APA Style

Erkihun, M., Asmare, Z., Endalamew, K., Getie, B., Kiros, T., & Berhan, A. (2024). Medical Scope of Biofilm and Quorum Sensing during Biofilm Formation: Systematic Review. Bacteria, 3(3), 118-135. https://doi.org/10.3390/bacteria3030008

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