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Effects of Low-Dose Amoxicillin on Staphylococcus aureus USA300 Biofilms

Mlynek, Kevin D ; Callahan, Mary T ; Shimkevitch, Anton V ; Farmer, Jackson T ; Endres, Jennifer L ; Marchand, Mélodie ; Bayles, Kenneth W ; Horswill, Alexander R ; Kaplan, Jeffrey B

Antimicrobial agents and chemotherapy, 2016-05, Vol.60 (5), p.2639-2651 [Periódico revisado por pares]

United States: American Society for Microbiology

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  • Título:
    Effects of Low-Dose Amoxicillin on Staphylococcus aureus USA300 Biofilms
  • Autor: Mlynek, Kevin D ; Callahan, Mary T ; Shimkevitch, Anton V ; Farmer, Jackson T ; Endres, Jennifer L ; Marchand, Mélodie ; Bayles, Kenneth W ; Horswill, Alexander R ; Kaplan, Jeffrey B
  • Assuntos: Amoxicillin ; Amoxicillin - pharmacology ; Anti-Bacterial Agents - pharmacology ; beta-Lactams - metabolism ; Biofilms ; Biofilms - drug effects ; Mechanisms of Action: Physiological Effects ; Methicillin-Resistant Staphylococcus aureus - drug effects ; Methicillin-Resistant Staphylococcus aureus - genetics ; Microbial Sensitivity Tests ; Staphylococcus aureus ; Staphylococcus aureus - drug effects ; Staphylococcus aureus - genetics
  • É parte de: Antimicrobial agents and chemotherapy, 2016-05, Vol.60 (5), p.2639-2651
  • Notas: ObjectType-Article-1
    SourceType-Scholarly Journals-1
    ObjectType-Feature-2
    content type line 23
    Present address: Kevin D. Mlynek, Department of Biology, Georgetown University, Washington, DC, USA; Mary T. Callahan, Department of Plant Science and Landscape Architecture, University of Maryland, College Park, Maryland, USA; Mélodie Marchand, Polytech Clermont Ferrand, Blaise Pascal University, Clermont-Ferrand, France.
    Citation Mlynek KD, Callahan MT, Shimkevitch AV, Farmer JT, Endres JL, Marchand M, Bayles KW, Horswill AR, Kaplan JB. 2016. Effects of low-dose amoxicillin on Staphylococcus aureus USA300 biofilms. Antimicrob Agents Chemother 60:2639–2651. doi:10.1128/AAC.02070-15.
  • Descrição: Previous studies showed that sub-MIC levels of β-lactam antibiotics stimulate biofilm formation in most methicillin-resistant Staphylococcus aureus (MRSA) strains. Here, we investigated this process by measuring the effects of sub-MIC amoxicillin on biofilm formation by the epidemic community-associated MRSA strain USA300. We found that sub-MIC amoxicillin increased the ability of USA300 cells to attach to surfaces and form biofilms under both static and flow conditions. We also found that USA300 biofilms cultured in sub-MIC amoxicillin were thicker, contained more pillar and channel structures, and were less porous than biofilms cultured without antibiotic. Biofilm formation in sub-MIC amoxicillin correlated with the production of extracellular DNA (eDNA). However, eDNA released by amoxicillin-induced cell lysis alone was evidently not sufficient to stimulate biofilm. Sub-MIC levels of two other cell wall-active agents with different mechanisms of action-d-cycloserine and fosfomycin-also stimulated eDNA-dependent biofilm, suggesting that biofilm formation may be a mechanistic adaptation to cell wall stress. Screening a USA300 mariner transposon library for mutants deficient in biofilm formation in sub-MIC amoxicillin identified numerous known mediators of S. aureus β-lactam resistance and biofilm formation, as well as novel genes not previously associated with these phenotypes. Our results link cell wall stress and biofilm formation in MRSA and suggest that eDNA-dependent biofilm formation by strain USA300 in low-dose amoxicillin is an inducible phenotype that can be used to identify novel genes impacting MRSA β-lactam resistance and biofilm formation.
  • Editor: United States: American Society for Microbiology
  • Idioma: Inglês
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