Special Issue "Microbial Biofilms"

A special issue of Pharmaceuticals (ISSN 1424-8247).

Deadline for manuscript submissions: closed (15 July 2015)

Special Issue Editor

Guest Editor
Dr. Dacheng Ren

Department of Biomedical and Chemical Engineering, Syracuse University, 329 Link Hall, Syracuse, NY 13244, USA
E-Mail
Interests: biofilm, antibiotic resistance, virulence, control, therapy

Special Issue Information

Dear Colleagues,

We welcome your submission to this Special Issue of Pharmaceuticals on the topic of Microbial Biofilms. It is well known that microbes are able to attach to both biotic and abiotic surfaces and form heterogeneous structures with microbial cells protected by an extracellular matrix secreted by these attached cells. These complex structures, known as biofilms, are ubiquitous and play important roles in chronic infections. Research in the past four decades has provided critical insights into biofilm physiology and the mechanism of antibiotic resistance. However, a lot more work is still needed to fully understand biofilm biology and associated persistence. Controlling these multicellular structures in clinical settings remains challenging and new therapies are urgently needed to treat biofilm infections. This special issue will focus on new developments in biofilm control using either new agents or through synergy between currently existing agents. Both in vitro and in vivo studies are encouraged.

Prof. Dacheng Ren
Guest Editor

Manuscript Submission Information

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Keywords

  • biofilm
  • antibiotic resistance
  • virulence
  • control
  • therapy

Published Papers (8 papers)

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Research

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Open AccessArticle Activity of Gallium Meso- and Protoporphyrin IX against Biofilms of Multidrug-Resistant Acinetobacter baumannii Isolates
Pharmaceuticals 2016, 9(1), 16; https://doi.org/10.3390/ph9010016
Received: 5 January 2016 / Revised: 12 March 2016 / Accepted: 15 March 2016 / Published: 17 March 2016
Cited by 6 | PDF Full-text (2715 KB) | HTML Full-text | XML Full-text
Abstract
Acinetobacter baumannii is a challenging pathogen due to antimicrobial resistance and biofilm development. The role of iron in bacterial physiology has prompted the evaluation of iron-modulation as an antimicrobial strategy. The non-reducible iron analog gallium(III) nitrate, Ga(NO3)3, has been [...] Read more.
Acinetobacter baumannii is a challenging pathogen due to antimicrobial resistance and biofilm development. The role of iron in bacterial physiology has prompted the evaluation of iron-modulation as an antimicrobial strategy. The non-reducible iron analog gallium(III) nitrate, Ga(NO3)3, has been shown to inhibit A. baumannii planktonic growth; however, utilization of heme-iron by clinical isolates has been associated with development of tolerance. These observations prompted the evaluation of iron-heme sources on planktonic and biofilm growth, as well as antimicrobial activities of gallium meso- and protoporphyrin IX (Ga-MPIX and Ga-PPIX), metal heme derivatives against planktonic and biofilm bacteria of multidrug-resistant (MDR) clinical isolates of A. baumannii in vitro. Ga(NO3)3 was moderately effective at reducing planktonic bacteria (64 to 128 µM) with little activity against biofilms (≥512 µM). In contrast, Ga-MPIX and Ga-PPIX were highly active against planktonic bacteria (0.25 to 8 µM). Cytotoxic effects in human fibroblasts were observed following exposure to concentrations exceeding 128 µM of Ga-MPIX and Ga-PPIX. We observed that the gallium metal heme conjugates were more active against planktonic and biofilm bacteria, possibly due to utilization of heme-iron as demonstrated by the enhanced effects on bacterial growth and biofilm formation. Full article
(This article belongs to the Special Issue Microbial Biofilms)
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Open AccessArticle Non-Monotonic Survival of Staphylococcus aureus with Respect to Ciprofloxacin Concentration Arises from Prophage-Dependent Killing of Persisters
Pharmaceuticals 2015, 8(4), 778-792; https://doi.org/10.3390/ph8040778
Received: 10 August 2015 / Revised: 2 November 2015 / Accepted: 6 November 2015 / Published: 17 November 2015
Cited by 3 | PDF Full-text (369 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Staphylococcus aureus is a notorious pathogen with a propensity to cause chronic, non-healing wounds. Bacterial persisters have been implicated in the recalcitrance of S. aureus infections, and this motivated us to examine the persistence of S. aureus to ciprofloxacin, a quinolone antibiotic. Upon [...] Read more.
Staphylococcus aureus is a notorious pathogen with a propensity to cause chronic, non-healing wounds. Bacterial persisters have been implicated in the recalcitrance of S. aureus infections, and this motivated us to examine the persistence of S. aureus to ciprofloxacin, a quinolone antibiotic. Upon treatment of exponential phase S. aureus with ciprofloxacin, we observed that survival was a non-monotonic function of ciprofloxacin concentration. Maximal killing occurred at 1 µg/mL ciprofloxacin, which corresponded to survival that was up to ~40-fold lower than that obtained with concentrations ≥ 5 µg/mL. Investigation of this phenomenon revealed that the non-monotonic response was associated with prophage induction, which facilitated killing of S. aureus persisters. Elimination of prophage induction with tetracycline was found to prevent cell lysis and persister killing. We anticipate that these findings may be useful for the design of quinolone treatments. Full article
(This article belongs to the Special Issue Microbial Biofilms)
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Open AccessArticle Controlling Persister and Biofilm Cells of Gram-Negative Bacteria with a New 1,3,5-Triazine Derivative
Pharmaceuticals 2015, 8(4), 696-710; https://doi.org/10.3390/ph8040696
Received: 28 July 2015 / Accepted: 28 September 2015 / Published: 10 October 2015
Cited by 10 | PDF Full-text (1675 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Infections caused by multidrug-resistant bacteria have been on the rise. This important issue presents a great challenge to the healthcare system and creates an urgent need for alternative therapeutic agents. As a potential solution to this problem, antimicrobial peptides (AMPs) have attracted increasing [...] Read more.
Infections caused by multidrug-resistant bacteria have been on the rise. This important issue presents a great challenge to the healthcare system and creates an urgent need for alternative therapeutic agents. As a potential solution to this problem, antimicrobial peptides (AMPs) have attracted increasing attention due to their broad spectrum of targeted microbes. However, most AMPs are expensive to synthesize, have relatively high cytotoxicity to mammalian cells, and are susceptible to proteolytic degradation. In order to overcome these limitations, novel synthetic AMPs are desired. Using 1,3,5-triazine (TN) as a template, several combinatorial libraries with varying cationic charge and lipophilicity were designed and screened by the Kallenbach lab. From this screening, TN-5 was identified as a potent lead. In the present study, this compound was tested for its antimicrobial activities on Escherichia coli and Pseudomonas aeruginosa. In addition to regular planktonic cells, the effects on biofilms and persister cells (metabolically inactive and antibiotic tolerant subpopulation) were also investigated. TN-5 was found to have a minimum inhibitory concentration (MIC) of 12.8 μM for both species and kill regular planktonic cells of both species dose dependently. TN-5 is also effective against persister cells of both E. coli and P. aeruginosa. The killing of biofilm cells of the mucoid P. aeruginosa PDO300 was enhanced by alginate lyase. Full article
(This article belongs to the Special Issue Microbial Biofilms)
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Open AccessArticle Antifungal Activity of 14-Helical β-Peptides against Planktonic Cells and Biofilms of Candida Species
Pharmaceuticals 2015, 8(3), 483-503; https://doi.org/10.3390/ph8030483
Received: 10 July 2015 / Revised: 29 July 2015 / Accepted: 4 August 2015 / Published: 13 August 2015
Cited by 13 | PDF Full-text (3151 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Candida albicans is the most prevalent cause of fungal infections and treatment is further complicated by the formation of drug resistant biofilms, often on the surfaces of implanted medical devices. In recent years, the incidence of fungal infections by other pathogenic Candida species [...] Read more.
Candida albicans is the most prevalent cause of fungal infections and treatment is further complicated by the formation of drug resistant biofilms, often on the surfaces of implanted medical devices. In recent years, the incidence of fungal infections by other pathogenic Candida species such as C. glabrata, C. parapsilosis and C. tropicalis has increased. Amphiphilic, helical β-peptide structural mimetics of natural antimicrobial α-peptides have been shown to exhibit specific planktonic antifungal and anti-biofilm formation activity against C. albicans in vitro. Here, we demonstrate that β-peptides are also active against clinically isolated and drug resistant strains of C. albicans and against other opportunistic Candida spp. Different Candida species were susceptible to β-peptides to varying degrees, with C. tropicalis being the most and C. glabrata being the least susceptible. β-peptide hydrophobicity directly correlated with antifungal activity against all the Candida clinical strains and species tested. While β-peptides were largely ineffective at disrupting existing Candida biofilms, hydrophobic β-peptides were able to prevent the formation of C. albicans, C. glabrata, C. parapsilosis and C. tropicalis biofilms. The broad-spectrum antifungal activity of β-peptides against planktonic cells and in preventing biofilm formation suggests the promise of this class of molecules as therapeutics. Full article
(This article belongs to the Special Issue Microbial Biofilms)
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Review

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Open AccessReview Control of Biofilms with the Fatty Acid Signaling Molecule cis-2-Decenoic Acid
Pharmaceuticals 2015, 8(4), 816-835; https://doi.org/10.3390/ph8040816
Received: 8 October 2015 / Revised: 11 November 2015 / Accepted: 18 November 2015 / Published: 25 November 2015
Cited by 16 | PDF Full-text (1275 KB) | HTML Full-text | XML Full-text
Abstract
Biofilms are complex communities of microorganisms in organized structures attached to surfaces. Importantly, biofilms are a major cause of bacterial infections in humans, and remain one of the most significant challenges to modern medical practice. Unfortunately, conventional therapies have shown to be inadequate [...] Read more.
Biofilms are complex communities of microorganisms in organized structures attached to surfaces. Importantly, biofilms are a major cause of bacterial infections in humans, and remain one of the most significant challenges to modern medical practice. Unfortunately, conventional therapies have shown to be inadequate in the treatment of most chronic biofilm infections based on the extraordinary innate tolerance of biofilms to antibiotics. Antagonists of quorum sensing signaling molecules have been used as means to control biofilms. QS and other cell-cell communication molecules are able to revert biofilm tolerance, prevent biofilm formation and disrupt fully developed biofilms, albeit with restricted effectiveness. Recently however, it has been demonstrated that Pseudomonas aeruginosa produces a small messenger molecule cis-2-decenoic acid (cis-DA) that shows significant promise as an effective adjunctive to antimicrobial treatment of biofilms. This molecule is responsible for induction of the native biofilm dispersion response in a range of Gram-negative and Gram-positive bacteria and in yeast, and has been shown to reverse persistence, increase microbial metabolic activity and significantly enhance the cidal effects of conventional antimicrobial agents. In this manuscript, the use of cis-2-decenoic acid as a novel agent for biofilm control is discussed. Stimulating the biofilm dispersion response as a novel antimicrobial strategy holds significant promise for enhanced treatment of infections and in the prevention of biofilm formation. Full article
(This article belongs to the Special Issue Microbial Biofilms)
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Open AccessReview Ecology of Anti-Biofilm Agents II: Bacteriophage Exploitation and Biocontrol of Biofilm Bacteria
Pharmaceuticals 2015, 8(3), 559-589; https://doi.org/10.3390/ph8030559
Received: 19 July 2015 / Revised: 30 August 2015 / Accepted: 2 September 2015 / Published: 9 September 2015
Cited by 21 | PDF Full-text (1893 KB) | HTML Full-text | XML Full-text
Abstract
Bacteriophages are the viruses of bacteria. In the guise of phage therapy they have been used for decades to successfully treat what are probable biofilm-containing chronic bacterial infections. More recently, phage treatment or biocontrol of biofilm bacteria has been brought back to the [...] Read more.
Bacteriophages are the viruses of bacteria. In the guise of phage therapy they have been used for decades to successfully treat what are probable biofilm-containing chronic bacterial infections. More recently, phage treatment or biocontrol of biofilm bacteria has been brought back to the laboratory for more rigorous assessment as well as towards the use of phages to combat environmental biofilms, ones other than those directly associated with bacterial infections. Considered in a companion article is the inherent ecological utility of bacteriophages versus antibiotics as anti-biofilm agents. Discussed here is a model for phage ecological interaction with bacteria as they may occur across biofilm-containing ecosystems. Specifically, to the extent that individual bacterial types are not highly abundant within biofilm-containing environments, then phage exploitation of those bacteria may represent a “Feast-or-famine” existence in which infection of highly localized concentrations of phage-sensitive bacteria alternate with treacherous searches by the resulting phage progeny virions for new concentrations of phage-sensitive bacteria to infect. An updated synopsis of the literature concerning laboratory testing of phage use to combat bacterial biofilms is then provided along with tips on how “Ecologically” such phage-mediated biofilm control can be modified to more reliably achieve anti-biofilm efficacy. Full article
(This article belongs to the Special Issue Microbial Biofilms)
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Open AccessReview Ecology of Anti-Biofilm Agents I: Antibiotics versus Bacteriophages
Pharmaceuticals 2015, 8(3), 525-558; https://doi.org/10.3390/ph8030525
Received: 19 July 2015 / Revised: 30 August 2015 / Accepted: 1 September 2015 / Published: 9 September 2015
Cited by 17 | PDF Full-text (1623 KB) | HTML Full-text | XML Full-text
Abstract
Bacteriophages, the viruses that infect bacteria, have for decades been successfully used to combat antibiotic-resistant, chronic bacterial infections, many of which are likely biofilm associated. Antibiotics as anti-biofilm agents can, by contrast, be inefficacious against even genetically sensitive targets. Such deficiencies in usefulness [...] Read more.
Bacteriophages, the viruses that infect bacteria, have for decades been successfully used to combat antibiotic-resistant, chronic bacterial infections, many of which are likely biofilm associated. Antibiotics as anti-biofilm agents can, by contrast, be inefficacious against even genetically sensitive targets. Such deficiencies in usefulness may result from antibiotics, as naturally occurring compounds, not serving their producers, in nature, as stand-alone disruptors of mature biofilms. Anti-biofilm effectiveness by phages, by contrast, may result from a combination of inherent abilities to concentrate lytic antibacterial activity intracellularly via bacterial infection and extracellularly via localized population growth. Considered here is the anti-biofilm activity of microorganisms, with a case presented for why, ecologically, bacteriophages can be more efficacious than traditional antibiotics as medically or environmentally applied biofilm-disrupting agents. Four criteria, it can be argued, generally must be met, in combination, for microorganisms to eradicate biofilms: (1) Furnishing of sufficiently effective antibacterial factors, (2) intimate interaction with biofilm bacteria over extended periods, (3) associated ability to concentrate antibacterial factors in or around targets, and, ultimately, (4) a means of physically disrupting or displacing target bacteria. In nature, lytic predators of bacteria likely can meet these criteria whereas antibiotic production, in and of itself, largely may not. Full article
(This article belongs to the Special Issue Microbial Biofilms)
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Graphical abstract

Other

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Open AccessCommentary Prospects for Anti-Biofilm Pharmaceuticals
Pharmaceuticals 2015, 8(3), 504-511; https://doi.org/10.3390/ph8030504
Received: 1 July 2015 / Revised: 21 August 2015 / Accepted: 24 August 2015 / Published: 27 August 2015
Cited by 6 | PDF Full-text (653 KB) | HTML Full-text | XML Full-text
Abstract
This commentary highlights several avenues currently being pursued in research labs to the development of new anti-biofilm pharmaceuticals. There is a real need for alternative therapeutic modalities for treating the persistent infections that sometimes form on implanted medical devices or compromised niches within [...] Read more.
This commentary highlights several avenues currently being pursued in research labs to the development of new anti-biofilm pharmaceuticals. There is a real need for alternative therapeutic modalities for treating the persistent infections that sometimes form on implanted medical devices or compromised niches within the body. Strategies being researched include discovering new antimicrobial agents that kill microorganisms in biofilms more effectively than do existing antibiotics, designing drugs that block microbial adhesion or interfere with intercellular communication, developing chemistries to disperse biofilms, and combining agents with different mechanisms of action. Though the need is great, the pathway to commercialization of new drugs is steep. One possible streamlined approach to navigating the regulatory approval process is to repurpose old drugs, a strategy that a few groups have shown can yield agents with anti-biofilm properties. Full article
(This article belongs to the Special Issue Microbial Biofilms)
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