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

Yu, Wen Liang; Hallinen, Kelsey M.; Wood, Kevin B.

doi:10.1128/aac.01603-17

Cited by 52 publications

(48 citation statements)

References 54 publications

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“…In addition, our experiments were performed in planktonic populations, while many of the high-inoculum infections requiring combination treatment are likely to involve surface-associated biofilms, where spatial heterogeneity and complex community dynamics can dramatically alter the response to antibiotics. In E. faecalis, for example, population density can significantly modulate growth dynamics [8], while sub-inhibitory doses of cell wall inhibitors may actually promote biofilm growth [62]. Recent work in other bacterial species also shows that evolutionary adaptation may differ between biofilm and planktonic communities [63,64].…”

Section: Discussionmentioning

confidence: 99%

Antibiotic interactions shape short-term evolution of resistance in E. faecalis

2020

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Antibiotic combinations are increasingly used to combat bacterial infections. Multidrug therapies are a particularly important treatment option for E. faecalis, an opportunistic pathogen that contributes to high-inoculum infections such as infective endocarditis. While numerous synergistic drug combinations for E. faecalis have been identified, much less is known about how different combinations impact the rate of resistance evolution. In this work, we use high-throughput laboratory evolution experiments to quantify adaptation in growth rate and drug resistance of E. faecalis exposed to drug combinations exhibiting different classes of interactions, ranging from synergistic to suppressive. We identify a wide range of evolutionary behavior, including both increased and decreased rates of growth adaptation, depending on the specific interplay between drug interaction and drug resistance profiles. For example, selection in a dual β-lactam combination leads to accelerated growth adaptation compared to selection with the individual drugs, even though the resulting resistance profiles are nearly identical. On the other hand, populations evolved in an aminoglycoside and β-lactam combination exhibit decreased growth adaptation and resistant profiles that depend on the specific drug concentrations. We show that the main qualitative features of these evolutionary trajectories can be explained by simple rescaling arguments that correspond to geometric transformations of the two-drug growth response surfaces measured in ancestral cells. The analysis also reveals multiple examples where resistance profiles selected by drug combinations are nearly growth-optimized along a contour connecting profiles selected by the component drugs. Our results highlight trade-offs between drug interactions and resistance profiles during the evolution of multi-drug resistance and emphasize evolutionary benefits and disadvantages of particular drug pairs targeting enterococci.

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Section: Discussionmentioning

confidence: 99%

Antibiotic interactions shape short-term evolution of resistance in E. faecalis

2020

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“…This effect was linked to autolysin-dependent release of eDNA, an important constituent of biofilms ( Kaplan et al, 2012 ). Likewise, Yu et al (2018) demonstrated that subinhibitory concentrations of bacterial cell-wall targeting antibiotics led to enhanced biofilm formation and increased density of biofilm cells in the prominent nosocomial pathogen E. faecalis . This effect was associated with increased cell lysis accompanied by a surge in eDNA levels, suggesting that such effects may take place in a variety of Gram-positive pathogens.…”

Section: Biofilms In Infectionsmentioning

confidence: 99%

Secondary Effects of Antibiotics on Microbial Biofilms

et al. 2020

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Biofilms are assemblages of microorganisms attached to each other, or to a surface, and encased in a protective, self-produced matrix. Such associations are now recognized as the predominant microbial growth mode. The physiology of cells in biofilms differs from that of the planktonic cells on which most research has been conducted. Consequently, there are significant gaps in our knowledge of the biofilm lifestyle. Filling this gap is particularly important, given that biofilm cells may respond differently to antibiotics than do planktonic cells of the same species. Understanding the effects of antibiotics on biofilms is of paramount importance for clinical practice due to the increased levels of antibiotic resistance and resistance dissemination in biofilms. From a wider environmental perspective antibiotic exposure can alter the ecology of biofilms in nature, and hence disrupt ecosystems. Biofilm cells display increased resilience toward antibiotics. This resilience is often explained by mechanisms and traits such as decreased antibiotic penetration, metabolically inactive persister cells, and intrinsic resistance by members of the biofilm community. Together, these factors suggest that cells in biofilms are often exposed to subinhibitory concentrations of antimicrobial agents. Here we discuss how cells in biofilms are affected by the presence of antibiotics at subinhibitory concentrations, and the possible ramifications of such secondary effects for healthcare and the environment.

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“…Biofilm formation of a clinical isolate of Enterococcus faecalis, which commonly underlies prosthetic valve endocarditis and multiple device infections, was also significantly increased by low concentrations of ampicillin, ceftriaxone, oxacillin, and fosfomycin. This enhancement of biofilm establishment appeared to be specific of molecules inhibiting cell wall synthesis (Yu et al, 2017). Additionally, a collection of ninety-six clinical isolates of S. epidermidis, which originate from various samples as wounds, catheters, sputum, etc., was recovered by He et al (2016).…”

Section: Induction Of Biofilm Formation By Antimicrobialsmentioning

confidence: 99%

Clinical Impact of Antibiotics for the Treatment of Pseudomonas aeruginosa Biofilm Infections

Olivares

Badel-Berchoux²,

Provot³

et al. 2020

Front. Microbiol.

133

110

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Bacterial biofilms are highly recalcitrant to antibiotic therapies due to multiple tolerance mechanisms. The involvement of Pseudomonas aeruginosa in a wide range of biofilmrelated infections often leads to treatment failures. Indeed, few current antimicrobial molecules are still effective on tolerant sessile cells. In contrast, studies increasingly showed that conventional antibiotics can, at low concentrations, induce a phenotype change in bacteria and consequently, the biofilm formation. Understanding the clinical effects of antimicrobials on biofilm establishment is essential to avoid the use of inappropriate treatments in the case of biofilm infections. This article reviews the current knowledge about bacterial growth within a biofilm and the preventive or inducer impact of standard antimicrobials on its formation by P. aeruginosa. The effect of antibiotics used to treat biofilms of other bacterial species, as Staphylococcus aureus or Escherichia coli, was also briefly mentioned. Finally, it describes two in vitro devices which could potentially be used as antibiotic susceptibility testing for adherent bacteria.

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

Cited by 52 publications

References 54 publications

Antibiotic interactions shape short-term evolution of resistance in E. faecalis

Antibiotic interactions shape short-term evolution of resistance in E. faecalis

Secondary Effects of Antibiotics on Microbial Biofilms

Clinical Impact of Antibiotics for the Treatment of Pseudomonas aeruginosa Biofilm Infections

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