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Genetic changes that correlate with the pine‐oil disinfectant‐reduced susceptibility mechanism of Staphylococcus aureus
Author(s) -
LamichhaneKhadka R.,
Riordan J.T.,
Delgado A.,
Muthaiyan A.,
Reynolds T.D.,
Wilkinson B.J.,
Gustafson J.E.
Publication year - 2008
Publication title -
journal of applied microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.889
H-Index - 156
eISSN - 1365-2672
pISSN - 1364-5072
DOI - 10.1111/j.1365-2672.2008.03956.x
Subject(s) - mutant , biology , microbiology and biotechnology , ccpa , staphylococcus aureus , biochemistry , gene , catabolite repression , bacteria , genetics
Aims: To identify factors associated with the Staphylococcus aureus pine‐oil disinfectant‐reduced‐susceptibility (PD RS ) mechanism and to describe one possible PD RS model. Methods and Results: Comparative genomic sequencing (CGS) and microarray analysis were utilized to detect mutations and transcriptome alterations that occur in a S. aureus PD RS mutant. Mutant analysis, antimicrobial gradient plates, growth studies and 3‐hydroxy‐3‐methylglutaryl coenzyme A synthase assays were then performed to confirm the biological consequences of the ‘omics’ alterations detected in a PD RS mutant. CGS uncovered three mutations in a PD RS mutant in a ( n ): alcohol dehydrogenase ( adh ), catabolite control protein A ( ccpA ) and an NADPH‐flavin oxidoreductase ( frp ). These mutations lead to increased growth rates; increased transcription of an NAD‐dependent d ‐lactate dehydrogenase gene ( ddh ); and increased flux through the mevalonate pathway. PD RS mutants demonstrated reduced susceptibility to bacitracin and farnesol, and one PD RS mutant displayed upregulation of bacA , a bacitracin‐resistance gene. Collectively, this evidence demonstrates altered undecaprenol metabolism in PD RS mutants. Conclusions: The PD RS mechanism proposed results from increased catabolic capabilities and increased flux through the mevalonate pathway as well as altered bactoprenol physiology. Significance and Impact of the Study: A novel mechanism that bacteria utilize to overcome the killing effects of PD formulations is proposed that is unique from the PD RS mechanism of the enterobacteraciae.