Small-Molecule Inhibition of Bacterial Biofilm

Ghosh, Anirban; Jayaraman, N; Chatterji, Dipankar

doi:10.1021/acsomega.9b03695

Cited by 97 publications

(67 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Our results with rats with chronic P. aeruginosa infection demonstrated that azithromycin significantly improved the pulmonary P. aeruginosa clearance, possibly by interfering with QS systems and crippling of the exopolysaccharides of the biofilm synthesized by the pel proteins. Besides inhibiting the virulence factors, azithromycin is known to have multiple effects against P. aeruginosa: (a) enhanced activity in the presence of serum, which could contribute to bacterial killing during chronic pulmonary infection (Lucchi et al, 2008), (b) anti-inflammatory activity that could help to reduce the inflammation at infection sites (Zeng et al, 2016;Zimmermann et al, 2018), (c) biofilm inhibitory or eradicative activity by modulating the synthesis of signaling molecules, such as the QS system, ci-di-GMP, and AHL (Favre-Bonte et al, 2003;Nalca et al, 2006;Barr et al, 2015;Ghosh et al, 2020), and (d) anti-virulence activity that could impair P. aeruginosa cells to produce extracellular biofilm matrix. These multiple effects of azithromycin could together be important mediators for its potent in vivo efficacy, or is there something else that drives the efficacy against P. aeruginosa in chronic CF patients?…”

Section: Discussionmentioning

confidence: 99%

Azithromycin Exhibits Activity Against Pseudomonas aeruginosa in Chronic Rat Lung Infection Model

Kumar¹,

Rao²,

Mathur³

et al. 2021

Front. Microbiol.

View full text Add to dashboard Cite

Pseudomonas aeruginosa forms biofilms in the lungs of chronically infected cystic fibrosis patients, which are tolerant to both the treatment of antibiotics and the host immune system. Normally, antibiotics are less effective against bacteria growing in biofilms; azithromycin has shown a potent efficacy in cystic fibrosis patients chronically infected with P. aeruginosa and improved their lung function. The present study was conducted to evaluate the effect of azithromycin on P. aeruginosa biofilm. We show that azithromycin exhibited a potent activity against P. aeruginosa biofilm, and microscopic observation revealed that azithromycin substantially inhibited the formation of solid surface biofilms. Interestingly, we observed that azithromycin restricted P. aeruginosa biofilm formation by inhibiting the expression of pel genes, which has been previously shown to play an essential role in bacterial attachment to solid-surface biofilm. In a rat model of chronic P. aeruginosa lung infection, we show that azithromycin treatment resulted in the suppression of quorum sensing-regulated virulence factors, significantly improving the clearance of P. aeruginosa biofilms compared to that in the placebo control. We conclude that azithromycin attenuates P. aeruginosa biofilm formation, impairs its ability to produce extracellular biofilm matrix, and increases its sensitivity to the immune system, which may explain the clinical efficacy of azithromycin in cystic fibrosis patients.

show abstract

Section: Discussionmentioning

confidence: 99%

Azithromycin Exhibits Activity Against Pseudomonas aeruginosa in Chronic Rat Lung Infection Model

Kumar¹,

Rao²,

Mathur³

et al. 2021

Front. Microbiol.

View full text Add to dashboard Cite

show abstract

“…For instance, a recent screening for quorum-quenching molecules led to the identification of small molecules able to inhibit the biofilm formation of C. albicans and S. apidermidis in polymicrobial biofilms [ 289 ]. In addition to quorum-sensing modulation, small molecule inhibitors of other enzymes and molecules were also investigated for their potential as anti-biofilm agents [ 290 ]. This includes molecules inhibiting the enzyme sortase A [ 169 , 170 , 171 , 172 ] and the use of surfactants, such as quaternary ammonium salts, in order to coat surfaces and prevent bacterial adhesion and biofilm formation.…”

Section: Alternative Treatments Of Staphylococcal Biofilmsmentioning

confidence: 99%

Staphylococcal Biofilms: Challenges and Novel Therapeutic Perspectives

et al. 2021

View full text Add to dashboard Cite

Staphylococci, like Staphylococcus aureus and S. epidermidis, are common colonizers of the human microbiota. While being harmless in many cases, many virulence factors result in them being opportunistic pathogens and one of the major causes of hospital-acquired infections worldwide. One of these virulence factors is the ability to form biofilms—three-dimensional communities of microorganisms embedded in an extracellular polymeric matrix (EPS). The EPS is composed of polysaccharides, proteins and extracellular DNA, and is finely regulated in response to environmental conditions. This structured environment protects the embedded bacteria from the human immune system and decreases their susceptibility to antimicrobials, making infections caused by staphylococci particularly difficult to treat. With the rise of antibiotic-resistant staphylococci, together with difficulty in removing biofilms, there is a great need for new treatment strategies. The purpose of this review is to provide an overview of our current knowledge of the stages of biofilm development and what difficulties may arise when trying to eradicate staphylococcal biofilms. Furthermore, we look into promising targets and therapeutic methods, including bacteriocins and phage-derived antibiofilm approaches.

show abstract

“…The virulence factors include those that are responsible for the overall growth and that contribute to biofilm formation [88]. The small-molecule inhibition approach is currently being widely investigated to target bacterial biofilms [89]. Antibiofilm strategies in Candida [90] and Escherichia [91] were recently reviewed by Cavalheiro et al and Verderosa et al, respectively.…”

Section: Other Strategiesmentioning

confidence: 99%

Mechanisms and Control Strategies of Antibiotic Resistance in Pathological Biofilms

Ying¹,

Yang²,

Zhang³

et al. 2021

J. Microbiol. Biotechnol.

View full text Add to dashboard Cite

Biofilms are protected microbial structures enclosed by a self-secreted extracellular matrix [1]. Bacteria biofilm is one of the most successful forms of life, being widely distributed in a diversity of environments [2]. All higher organisms (including humans) are colonized by microorganisms that form biofilms, mostly bacteria [3]. The ability of biofilms to escape the host immune system and resist antibiotics poses great health threats to patients [4,5].Biofilm formation contributes to drug resistance and inflammation, causing persistent infections in patients [6]. Biofilms also function as cell reservoirs that can repopulate infection sites after the release of suppression. For example, biofilm formation is a major concern for cystic fibrosis pneumonia caused by Pseudomonas aeruginosa and urinary tract infections caused by Escherichia coli, both of which are refractory to multiple antibiotics [7]. Therefore, basic research on biofilm formation and the mechanism of their resistance is of great clinical relevance. The objective of this review is to summarize the current research progress in antibiotic resistance mechanisms associated with bacterial biofilms and anti-biofilm strategies, which may greatly benefit patients who suffer from biofilm-related infections. Bacterial Biofilms Structure and Characteristics of Bacterial BiofilmThe physical scaffold of a biofilm is the matrix of extracellular polymeric substances (EPSs), self-secreted substances that keep bacterial cells in a contained structure and attach them to surfaces [8]. Most of the biomass of the biofilm is hydrated EPS rather than bacterial cells, which only make up between 2% to 15% of the total biofilm mass [9]. EPS is mostly composed of polysaccharides, proteins, lipids and extracellular DNA (eDNA) (Fig. 1) [9]. Enhanced antimicrobial resistance, nutrient capture and social cooperation are three main characteristic features of biofilms, and the EPS matrix underlies these important properties [2]. The structures of biofilms somewhat resembles tissues of higher organisms, which are structurally complex and highly heterogenous in gene expression [10], both contributing to the resistance mechanisms of biofilm. Life Cycle of Bacterial BiofilmsThe transition from planktonic growth to biofilm is a complex and highly regulated process that follows a few steps (Fig. 1). The first step is the initial attachment of planktic bacterial cells to a surface, which often happens when cells are under environmental stress. The propelling structures, such as appendages, fimbriae and sex pili, Bacterial biofilm is a community of bacteria that are embedded and structured in a self-secreted extracellular matrix. An important clinical-related characteristic of bacterial biofilms is that they are much more resistant to antimicrobial agents than the planktonic cells (up to 1,000 times), which is one of the main causes of antibiotic resistance in clinics. Therefore, infections caused by biofilms are notoriously difficult to eradicate, such as lung infection caused by Pseudom...

show abstract

Small-Molecule Inhibition of Bacterial Biofilm

Cited by 97 publications

References 25 publications

Azithromycin Exhibits Activity Against Pseudomonas aeruginosa in Chronic Rat Lung Infection Model

Azithromycin Exhibits Activity Against Pseudomonas aeruginosa in Chronic Rat Lung Infection Model

Staphylococcal Biofilms: Challenges and Novel Therapeutic Perspectives

Mechanisms and Control Strategies of Antibiotic Resistance in Pathological Biofilms

Contact Info

Product

Resources

About