Sub-inhibitory membrane damage undermines Staphylococcus aureus virulence

Publication date: Available online 8 April 2019Source: Biochimica et Biophysica Acta (BBA) - BiomembranesAuthor(s): Ayelet Sarah Hershkovits, Igor Pozdnyakov, Ohad Meir, Amram MorAbstractWe investigated antibacterial properties of a recently described membrane-active lipopeptide, C10OOc12O (decanoyl-ornithyl-ornithyl-dodecanoyl-ornithyl-amide) against Gram-positive bacteria (GPB). Minimal inhibitory concentrations (MICs) and kinetics were compared in culture media and plasma. Chemo-sensitization to antibiotics was determined using the checkerboard assay. Membrane damages were estimated using diverse membrane potential sensitive dyes. ATP levels and relevant enzymes activities were measured using commercial bioassay kits.While relatively weakly active in simple culture media, sub-MIC levels (~ten-fold) of C10OOc12O have significantly improved the antibacterial function of Human plasma. Mechanistic studies indicated that C10OOc12O-treated bacteria have sustained mild membrane damage(s) in association with rapid (within 2 min) but low (<10%) dissipation of the trans-membrane potential; Intracellular ATP levels were transiently reduced (~20%) whereas extracellular ATP increased only at MIC values; Sub-inhibitory concentrations were sufficient for inhibiting major agr-regulated virulence factors (lipase and α-toxin) and for sensitizing MRSA USA300 to the antibiotic oxacillin to the point of reverting the bacteria status from oxacillin-resistant to oxacillin-sensitive (i.e.,...
Source: Biochimica et Biophysica Acta (BBA) Biomembranes - Category: Biochemistry Source Type: research