Microbial Biofilms: From Molecular Mechanisms and Structure to Antimicrobial Therapy

A special issue of Microorganisms (ISSN 2076-2607). This special issue belongs to the section "Biofilm".

Deadline for manuscript submissions: closed (30 June 2022) | Viewed by 14316

Special Issue Editors

Department of Biosciences, University of Milan, 20133 Milan, Italy
Interests: microbial adhesion; gene expression; transcription regulation; antimetabolite drugs; host–pathogen interaction
CSIC-GN- Instituto de Agrobiotecnologia (IDAB), 31192 Pamplona, Spain
Interests: molecular interactions; surface proteins; extracellular matrix; antibiotic resistance; amyloids

Special Issue Information

Dear Colleagues,

The study of microbial biofilms represents a thriving field in every aspect of microbiology, as biofilms play a pivotal role in medical microbiology, environmental microbiology, and microbial biotechnology alike. The investigation of the basic molecular mechanisms leading to biofilm formation, maintenance, and break-up, in different microorganisms, has led to the discovery of some of the most sophisticated signaling and regulatory pathways known to exist in the microbial world.

What we find really fascinating about microbial biofilms is how complex their impact is on human life and activities, and how multifaceted their nature can be in different contexts. To offer a health-related example, it has been estimated that 65% of overall bacterial infections are caused by, or associated with, biofilms, yet a switch from single cell to biofilm is often linked to an overall reduction in production of virulence factors in pathogenic bacteria, and it sometimes constitutes the transition from an acute to a chronic infection. Bacteria in biofilms do not respond to antibiotic therapy as planktonic organisms of the same species do, by activating tolerance mechanisms to antibiotics that differ from bacterial resistance via mutations. These observations eventually led to the definition of bacterial persistence, which in turn introduced the concept of epigenetic mechanisms to the bacterial world and has highlighted how the killing effect of antimicrobial agents is often mediated by mechanisms more complex than simple target inhibition.

In this Special Issue of Microorganisms, we invite scientists with an interest in microbial (i.e., both bacterial and fungal) biofilms to send contributions concerning any aspect related to this field: from the role of mixed biofilms in different ecological niches, including industrial settings and complex microbial communities associated with the human body, to development of novel antimicrobial agents with antibiofilm activity, to investigations on microbial virulence linked to biofilm formation, to the basic regulatory mechanisms presiding over the various steps of the biofilm/planktonic cells cycle, to investigations on the impact of microbial biofilms on human health.

Prof. Dr. Paolo Landini
Dr. Jaione Valle
Guest Editors

Manuscript Submission Information

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Keywords

  • microbial biofilms
  • microbial communities
  • antimicrobial agents
  • virulence
  • adhesion factors
  • host–pathogen interaction
  • bacterial persistence

Published Papers (6 papers)

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Editorial

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3 pages, 192 KiB  
Editorial
Microbial Biofilms: From Molecular Mechanisms and Structure to Antimicrobial Therapy
Microorganisms 2022, 10(8), 1638; https://doi.org/10.3390/microorganisms10081638 - 12 Aug 2022
Viewed by 885
Abstract
The first published observations that microorganisms associate to form microbial communities structured as biofilms in natural environments date back to the first half of the last century [...] Full article

Research

Jump to: Editorial

17 pages, 5668 KiB  
Article
Lack of Direct Correlation between Biofilm Formation and Antimicrobial Resistance in Clinical Staphylococcus epidermidis Isolates from an Italian Hospital
Microorganisms 2022, 10(6), 1163; https://doi.org/10.3390/microorganisms10061163 - 06 Jun 2022
Cited by 6 | Viewed by 1856
Abstract
Staphylococcus epidermidis is an opportunistic pathogen and a frequent cause of nosocomial infections. In this work, we show that, among 51 S. epidermidis isolates from an Italian hospital, only a minority displayed biofilm formation, regardless of their isolation source (peripheral blood, catheter, or [...] Read more.
Staphylococcus epidermidis is an opportunistic pathogen and a frequent cause of nosocomial infections. In this work, we show that, among 51 S. epidermidis isolates from an Italian hospital, only a minority displayed biofilm formation, regardless of their isolation source (peripheral blood, catheter, or skin wounds); however, among the biofilm-producing isolates, those from catheters were the most efficient in biofilm formation. Interestingly, most isolates including strong biofilm producers displayed production levels of PIA (polysaccharide intercellular adhesin), the main S. epidermidis extracellular polysaccharide, similar to reference S. epidermidis strains classified as non-biofilm formers, and much lower than those classified as intermediate or high biofilm formers, possibly suggesting that high levels of PIA production do not confer a particular advantage for clinical isolates. Finally, while for the reference S. epidermidis strains the biofilm production clearly correlated with the decreased sensitivity to antibiotics, in particular, protein synthesis inhibitors, in our clinical isolates, such positive correlation was limited to tetracycline. In contrast, we observed an inverse correlation between biofilm formation and the minimal inhibitory concentrations for levofloxacin and teicoplanin. In addition, in growth conditions favoring PIA production, the biofilm-forming isolates showed increased sensitivity to daptomycin, clindamycin, and erythromycin, with increased tolerance to the trimethoprim/sulfamethoxazole association. The lack of direct correlation between the biofilm production and increased tolerance to antibiotics in S. epidermidis isolates from a clinical setting would suggest, at least for some antimicrobials, the possible existence of a trade-off between the production of biofilm determinants and antibiotic resistance. Full article
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14 pages, 1417 KiB  
Article
Essential Oils Biofilm Modulation Activity and Machine Learning Analysis on Pseudomonas aeruginosa Isolates from Cystic Fibrosis Patients
Microorganisms 2022, 10(5), 887; https://doi.org/10.3390/microorganisms10050887 - 24 Apr 2022
Cited by 11 | Viewed by 3533
Abstract
The opportunistic pathogen Pseudomonas aeruginosa is often involved in airway infections of cystic fibrosis (CF) patients. It persists in the hostile CF lung environment, inducing chronic infections due to the production of several virulence factors. In this regard, the ability to form a [...] Read more.
The opportunistic pathogen Pseudomonas aeruginosa is often involved in airway infections of cystic fibrosis (CF) patients. It persists in the hostile CF lung environment, inducing chronic infections due to the production of several virulence factors. In this regard, the ability to form a biofilm plays a pivotal role in CF airway colonization by P. aeruginosa. Bacterial virulence mitigation and bacterial cell adhesion hampering and/or biofilm reduced formation could represent a major target for the development of new therapeutic treatments for infection control. Essential oils (EOs) are being considered as a potential alternative in clinical settings for the prevention, treatment, and control of infections sustained by microbial biofilms. EOs are complex mixtures of different classes of organic compounds, usually used for the treatment of upper respiratory tract infections in traditional medicine. Recently, a wide series of EOs were investigated for their ability to modulate biofilm production by different pathogens comprising S. aureus, S. epidermidis, and P. aeruginosa strains. Machine learning (ML) algorithms were applied to develop classification models in order to suggest a possible antibiofilm action for each chemical component of the studied EOs. In the present study, we assessed the biofilm growth modulation exerted by 61 commercial EOs on a selected number of P. aeruginosa strains isolated from CF patients. Furthermore, ML has been used to shed light on the EO chemical components likely responsible for the positive or negative modulation of bacterial biofilm formation. Full article
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16 pages, 2067 KiB  
Article
Experimental Polymorphism Survey in Intergenic Regions of the icaADBCR Locus in Staphylococcus aureus Isolates from Periprosthetic Joint Infections
Microorganisms 2022, 10(3), 600; https://doi.org/10.3390/microorganisms10030600 - 10 Mar 2022
Cited by 7 | Viewed by 1992
Abstract
Staphylococcus aureus is a leading cause of prosthetic joint infections (PJI) characterized by bacterial biofilm formation and recalcitrance to immune-mediated clearance and antibiotics. The molecular events behind PJI infection are yet to be unraveled. In this sense, identification of polymorphisms in bacterial genomes [...] Read more.
Staphylococcus aureus is a leading cause of prosthetic joint infections (PJI) characterized by bacterial biofilm formation and recalcitrance to immune-mediated clearance and antibiotics. The molecular events behind PJI infection are yet to be unraveled. In this sense, identification of polymorphisms in bacterial genomes may help to establish associations between sequence variants and the ability of S. aureus to cause PJI. Here, we report an experimental nucleotide-level survey specifically aimed at the intergenic regions (IGRs) of the icaADBCR locus, which is responsible for the synthesis of the biofilm exopolysaccharide PIA/PNAG, in a collection of strains sampled from PJI and wounds. IGRs of the icaADBCR locus were highly conserved and no PJI-specific SNPs were found. Moreover, polymorphisms in these IGRs did not significantly affect transcription of the icaADBC operon under in vitro laboratory conditions. In contrast, an SNP within the icaR coding region, resulting in a V176E change in the transcriptional repressor IcaR, led to a significant increase in icaADBC operon transcription and PIA/PNAG production and a reduction in S. aureus virulence in a Galleria mellonella infection model. In conclusion, SNPs in icaADBCR IGRs of S. aureus isolates from PJI are not associated with icaADBC expression, PIA/PNAG production and adaptation to PJI. Full article
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15 pages, 1961 KiB  
Article
Inactivation of the Pyrimidine Biosynthesis pyrD Gene Negatively Affects Biofilm Formation and Virulence Determinants in the Crohn’s Disease-Associated Adherent Invasive Escherichia coli LF82 Strain
Microorganisms 2022, 10(3), 537; https://doi.org/10.3390/microorganisms10030537 - 28 Feb 2022
Cited by 4 | Viewed by 2995
Abstract
In Crohn’s disease (CD) patients, the adherent-invasive Escherichia coli (AIEC) pathovar contributes to the chronic inflammation typical of the disease via its ability to invade gut epithelial cells and to survive in macrophages. We show that, in the AIEC strain LF82, inactivation of [...] Read more.
In Crohn’s disease (CD) patients, the adherent-invasive Escherichia coli (AIEC) pathovar contributes to the chronic inflammation typical of the disease via its ability to invade gut epithelial cells and to survive in macrophages. We show that, in the AIEC strain LF82, inactivation of the pyrD gene, encoding dihydroorotate dehydrogenase (DHOD), an enzyme of the de novo pyrimidine biosynthetic pathway, completely abolished its ability of to grow in a macrophage environment-mimicking culture medium. In addition, pyrD inactivation reduced flagellar motility and strongly affected biofilm formation by downregulating transcription of both type 1 fimbriae and curli subunit genes. Thus, the pyrD gene appears to be essential for several cellular processes involved in AIEC virulence. Interestingly, vidofludimus (VF), a DHOD inhibitor, has been proposed as an effective drug in CD treatment. Despite displaying a potentially similar binding mode for both human and E. coli DHOD in computational molecular docking experiments, VF showed no activity on either growth or virulence-related processes in LF82. Altogether, our results suggest that the crucial role played by the pyrD gene in AIEC virulence, and the presence of structural differences between E. coli and human DHOD allowing for the design of specific inhibitors, make E. coli DHOD a promising target for therapeutical strategies aiming at counteracting chronic inflammation in CD by acting selectively on its bacterial triggers. Full article
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14 pages, 2082 KiB  
Article
Multi-Omics Reveals the Inhibition of Lactiplantibacillus plantarum CCFM8724 in Streptococcus mutans-Candida albicans Mixed-Species Biofilms
Microorganisms 2021, 9(11), 2368; https://doi.org/10.3390/microorganisms9112368 - 16 Nov 2021
Cited by 9 | Viewed by 2162
Abstract
Lactiplantibacillus plantarum CCFM8724 is a probiotic with the potential to prevent dental caries in vitro and in vivo. To explore the effects of this probiotic at inhibiting Streptococcus mutans-Candida albicans mixed-species biofilm and preventing dental caries, multi-omics, including metabolomics and transcriptomics, [...] Read more.
Lactiplantibacillus plantarum CCFM8724 is a probiotic with the potential to prevent dental caries in vitro and in vivo. To explore the effects of this probiotic at inhibiting Streptococcus mutans-Candida albicans mixed-species biofilm and preventing dental caries, multi-omics, including metabolomics and transcriptomics, was used to investigate the regulation of small-molecule metabolism during biofilm formation and the gene expression in the mixed-species biofilm. Metabolomic analysis revealed that some carbohydrates related to biofilm formation, such as sucrose, was detected at lower levels due to the treatment with the L. plantarum supernatant. Some sugar alcohols, such as xylitol and sorbitol, were detected at higher levels, which may have inhibited the growth of S. mutans. In transcriptomic analysis, the expression of the virulence genes of C. albicans, such as those that code agglutinin-like sequence (Als) proteins, was affected. In addition, metabolomics coupled with a Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis and RNA-seq revealed that the L. plantarum supernatant had an active role in sugar metabolism during the formation of the S. mutans-C. albicans mixed-species biofilm, and the L. plantarum supernatant was also related to carbohydrate utilization, glucan biosynthesis, and mycelium formation. Hence, L. plantarum CCFM8724 decreased the mixed-species biofilm mass from the perspective of gene expression and metabolic reprogramming. Our results provide a rationale for evaluating L. plantarum CCFM8724 as a potential oral probiotic for inhibiting cariogenic pathogen biofilm formation and improving dental caries. Full article
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