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dc.contributor.authorBayer, Arnold S
dc.contributor.authorKupferwasser, L I
dc.contributor.authorBrown, Melissa Hackett
dc.contributor.authorSkurray, Ronald Anthony
dc.contributor.authorGrkovic, Steve
dc.contributor.authorJones, T
dc.contributor.authorMukhopadhay, K
dc.contributor.authorYeaman, M R
dc.date.accessioned2010-07-27T05:53:32Z
dc.date.available2010-07-27T05:53:32Z
dc.date.issued2006en_US
dc.identifier.citationBayer, A.S., Kupferwasser, L.I., Brown, M.H., Skurray, R.A., Grkovic, S., Jones, T., Mukhopadhay, K., & Yeaman, M.R., 2006. Low-level resistance of staphylococcus aureus to thrombin-induced platelet microbicidal protein 1 in vitro associated with qacA gene carriage is independent of multidrug efflux pump activity. Antimicrobial Agents and Chemotherapy, 50(7), 2448-2454.en
dc.identifier.issn0066-4804
dc.identifier.urihttp://hdl.handle.net/2328/9311
dc.description.abstractThrombin-induced platelet microbial protein 1 (tPMP-1), a cationic antimicrobial polypeptide released from thrombin-stimulated rabbit platelets, targets the Staphylococcus aureus cytoplasmic membrane to initiate its microbicidal effects. In vitro resistance to tPMP-1 correlates with survival advantages in vivo. In S. aureus, the plasmid-carried qacA gene encodes a multi-drug transporter, conferring resistance to organic cations (e.g., ethidium [Et]) via proton motive force (PMF)-energized export. We previously showed that qacA also confers a tPMP-1-resistant (tPMP-1r) phenotype in vitro. The current study evaluated whether (i) transporters encoded by the qacB and qacC multidrug resistance genes also confer tPMP-1r and (ii) tPMP-1r mediated by qacA is dependent on efflux pump activity. In contrast to tPMP-1r qacA-bearing strains, the parental strain and its isogenic qacB- and qacC-containing strains were tPMP-1 susceptible (tPMP-1s). Efflux pump inhibition by cyanide m-chlorophenylhydrazone abrogated Etr, but not tPMP-1r, in the qacA-bearing strain. In synergy assays, exposure of the qacA-bearing strain to tPMP-1 did not affect the susceptibility of Et (ruling out Et–tPMP-1 cotransport). The following cytoplasmic membrane parameters did not differ significantly between the qacA-bearing and parental strains: contents of the major phospholipids; asymmetric distributions of the positively charged species, lysyl-phosphotidylglycerol; fatty acid composition; and relative surface charge. Of note, the qacA-bearing strain exhibited greater membrane fluidity than that of the parental, qacB-, or qacC-bearing strain. In conclusion, among these families of efflux pumps, only the multi-drug transporter encoded by qacA conferred a tPMP-1r phenotype. These data suggest that qacA-encoded tPMP-1r results from the impact of a specific transporter upon membrane structure or function unrelated to PMF-dependent peptide efflux.en
dc.titleLow-level resistance of staphylococcus aureus to thrombin-induced platelet microbicidal protein 1 in vitro associated with qacA gene carriage is independent of multidrug efflux pump activityen
dc.typeArticleen
dc.identifier.rmid2006004336
dc.identifier.doihttps://doi.org/10.1128/AAC.00028-06en
dc.subject.forgroup1108 Medical Microbiologyen
dc.subject.forgroup0605 Microbiologyen
local.contributor.authorOrcidLookupBrown, Melissa Hackett: https://orcid.org/0000-0001-6461-7550en_US


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