Influence of a subinhibitory concentration of vancomycin on the in vitro expression of virulence-related genes in the vancomycin-resistant Enterococcus faecalis

Moura, Tiane Martin de; Campos, Fabrício Souza; Caierão, Juliana; Franco, Ana Cláudia; Roehe, Paulo Michel; d’Azevedo, Pedro Alves; Frazzon, Jeverson; Frazzon, Ana Paula Guedes

doi:10.1590/0037-8682-0017-2015

Cited by 10 publications

(7 citation statements)

References 14 publications

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“…Antibiotics modulate bacterial physiology regarding bacterial growth, gene transcription, and toxin production at subinhibitory concentrations (Goh et al, 2002; Yim et al, 2011; Moura et al, 2015; Ramos et al, 2015; Sinel et al, 2017). This study demonstrates that antibiotics at subinhibitory concentrations can modulate the biogenesis and proteomes of MVs in E. faecium .…”

Section: Discussionmentioning

confidence: 99%

Production of Membrane Vesicles by Enterococcus faecium Cultured With or Without Subinhibitory Concentrations of Antibiotics and Their Pathological Effects on Epithelial Cells

Kim

Son

et al. 2019

Front. Cell. Infect. Microbiol.

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Enterococcus faecium is a clinically important pathogen associated with opportunistic infection and multi-drug resistance. E. faecium has been shown to produce membrane vesicles (MVs), but MV production by E. faecium under antibiotic stress conditions and the pathogenic traits thereof have yet to be determined. This study investigated the production of MVs in E. faecium ATCC 700221 cultured with sub-minimum inhibitory concentrations (MICs) of vancomycin or linezolid and determined their pathologic effects on colon epithelial Caco-2 cells. E. faecium ATCC 700221 cultured with 1/2 MIC of vancomycin or linezolid produced 3.0 and 1.5 times more MV proteins than bacteria cultured without antibiotics, respectively. Totals of 438, 461, and 513 proteins were identified in MVs from E. faecium cultured in brain heart infusion broth (MVs/BHI), BHI broth with 1/2 MIC of vancomycin (MVs/VAN), or BHI broth with 1/2 MIC of linezolid (MVs/LIN), respectively. Intact MVs/BHI induced cytotoxicity and the expression of pro-inflammatory cytokine and chemokine genes in Caco-2 cells in a dose-dependent manner, but proteinase K-treated MVs significantly suppressed these pro-inflammatory responses. MVs/LIN were more cytotoxic toward Caco-2 cells than MVs/BHI and MVs/VAN, whereas MVs/VAN stimulated more pro-inflammatory cytokine gene expression in Caco-2 cells than MVs/BHI and MVs/LIN. Overall results indicated that antibiotics modulate the biogenesis and proteomes of MVs in E. faecium at subinhibitory concentrations. MVs produced by E. faecium cultured under antibiotic stress conditions induce strong host cell responses that may contribute to the pathogenesis E. faecium .

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Section: Discussionmentioning

confidence: 99%

Production of Membrane Vesicles by Enterococcus faecium Cultured With or Without Subinhibitory Concentrations of Antibiotics and Their Pathological Effects on Epithelial Cells

Kim

Son

et al. 2019

Front. Cell. Infect. Microbiol.

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“…For example, recent work has shown that eDNA is prevalent in biofilms even at the early developmental stages when cell lysis is minimal ( 29 ), and it is possible that subinhibitory drug concentrations increase eDNA levels through similar nonlytic mechanisms. In addition, it is well known that sub-MIC levels of antibiotic can dramatically alter gene expression profiles in bacteria ( 37 – 39 ), indicating that biofilm enhancement may arise from a complex combination of multiple factors. Finally, we note that live-dead cell staining results should be interpreted with some caution, because uptake of various stains may be variable ( 40 – 44 ).…”

Section: Discussionmentioning

confidence: 99%

Interplay between Antibiotic Efficacy and Drug-Induced Lysis Underlies Enhanced Biofilm Formation at Subinhibitory Drug Concentrations

Hallinen

Wood

2018

Antimicrob Agents Chemother

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Subinhibitory concentrations of antibiotics have been shown to enhance biofilm formation in multiple bacterial species. While antibiotic exposure has been associated with modulated expression of many biofilm-related genes, the mechanisms of drug-induced biofilm formation remain a focus of ongoing research efforts and may vary significantly across species. In this work, we investigate antibiotic-induced biofilm formation in Enterococcus faecalis, a leading cause of nosocomial infections. We show that biofilm formation is enhanced by subinhibitory concentrations of cell wall synthesis inhibitors but not by inhibitors of protein, DNA, folic acid, or RNA synthesis. Furthermore, enhanced biofilm is associated with increased cell lysis, increases in extracellular DNA (eDNA) levels, and increases in the density of living cells in the biofilm. In addition, we observe similar enhancement of biofilm formation when cells are treated with nonantibiotic surfactants that induce cell lysis. These findings suggest that antibiotic-induced biofilm formation is governed by a trade-off between drug toxicity and the beneficial effects of cell lysis. To understand this trade-off, we developed a simple mathematical model that predicts changes in antibiotic-induced biofilm formation due to external perturbations, and we verified these predictions experimentally. Specifically, we demonstrate that perturbations that reduce eDNA (DNase treatment) or decrease the number of living cells in the planktonic phase (a second antibiotic) decrease biofilm induction, while chemical inhibitors of cell lysis increase relative biofilm induction and shift the peak to higher antibiotic concentrations. Overall, our results offer experimental evidence linking cell wall synthesis inhibitors, cell lysis, increased eDNA levels, and biofilm formation in E. faecalis while also providing a predictive quantitative model that sheds light on the interplay between cell lysis and antibiotic efficacy in developing biofilms.

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“…Although it is known some antibiotics that inhibit protein biosynthesis in sub-inhibitory concentrations induce biofilm formation (Hoffman et al, 2005). There is also evidence that sub-inhibitory concentrations of glycopeptide vancomycin [cellular target is lipid II (De Moura et al, 2015)] change the expression of a several genes associated with virulence E. faecalis (Breukink and de Kruijff, 2006).…”

Section: Antimicrobial Peptides As Signaling Moleculesmentioning

confidence: 99%

Sub-inhibitory Effects of Antimicrobial Peptides

Vasilchenko

Рогожин

2019

Front. Microbiol.

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Antimicrobials, and particularly antimicrobial peptides (AMPs), have been thoroughly studied due to their therapeutic potential. The research on their exact mode of action on bacterial cells, especially at under sublethal concentrations, has resulted in a better understanding of the unpredictable nature of bacterial behavior under stress conditions. In this review, we were aiming to gather the wide yet still under-investigated knowledge about various AMPs and their subinhibition effects on cellular and molecular levels. We describe how AMP action is non-linear and unpredictable, also showing that exposure to AMP can lead to antimicrobial resistance via triggering various regulatory systems. Being one of the most known types of antimicrobials, bacteriocins have dual action and can also be utilized by microorganisms as signaling molecules at naturally achievable sub-inhibitory concentrations. The unpredictable nature of AMP action and the pathogenic response triggered by them remains an area of knowledge that requires further investigation.

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Influence of a subinhibitory concentration of vancomycin on the in vitro expression of virulence-related genes in the vancomycin-resistant Enterococcus faecalis

Cited by 10 publications

References 14 publications

Production of Membrane Vesicles by Enterococcus faecium Cultured With or Without Subinhibitory Concentrations of Antibiotics and Their Pathological Effects on Epithelial Cells

Production of Membrane Vesicles by Enterococcus faecium Cultured With or Without Subinhibitory Concentrations of Antibiotics and Their Pathological Effects on Epithelial Cells

Interplay between Antibiotic Efficacy and Drug-Induced Lysis Underlies Enhanced Biofilm Formation at Subinhibitory Drug Concentrations

Sub-inhibitory Effects of Antimicrobial Peptides

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