title: Global analysis of the Staphylococcus aureus response to mupirocin.
abstract: In the present study, we analyzed the response of S. aureus to mupirocin, the drug of choice for nasal decolonization. Mupirocin selectively inhibits the bacterial isoleucyl-tRNA synthetase (IleRS), leading to the accumulation of uncharged isoleucyl-tRNA and eventually the synthesis of (p)ppGpp. The alarmone (p)ppGpp induces the stringent response, an important global transcriptional and translational control mechanism that allows bacteria to adapt to nutritional deprivation. To identify proteins with an altered synthesis pattern in response to mupirocin treatment, we used the highly sensitive 2-dimensional gel electrophoresis technique in combination with mass spectrometry. The results were complemented by DNA microarray, Northern blot, and metabolome analyses. Whereas expression of genes involved in nucleotide biosynthesis, DNA metabolism, energy metabolism, and translation was significantly downregulated, expression of isoleucyl-tRNA synthetase, the branched-chain amino acid pathway, and genes with functions in oxidative-stress resistance (ahpC and katA) and putative roles in stress protection (the yvyD homologue SACOL0815 and SACOL1759 and SACOL2131) and transport processes was increased. A comparison of the regulated genes to known regulons suggests the involvement of the global regulators CodY and SigB in shaping the response of S. aureus to mupirocin. Of particular interest was the induced transcription of genes encoding virulence-associated regulators (i.e., arlRS, saeRS, sarA, sarR, sarS, and sigB), as well as genes directly involved in the virulence of S. aureus (i.e., fnbA, epiE, epiG, and seb).
authors: Institut für Mikrobiologie, Ernst-Moritz-Arndt-Universität, Greifswald, Germany.
authors: Swantje
authors: S
authors: Reiss
authors: Jan
authors: J
authors: Pané-Farré
authors: Stephan
authors: S
authors: Fuchs
authors: Patrice
authors: P
authors: François
authors: Manuel
authors: M
authors: Liebeke
authors: Jacques
authors: J
authors: Schrenzel
authors: Ulrike
authors: U
authors: Lindequist
authors: Michael
authors: M
authors: Lalk
authors: Christiane
authors: C
authors: Wolz
authors: Michael
authors: M
authors: Hecker
authors: Susanne
authors: S
authors: Engelmann
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D015180:Electrophoresis, Gel, Two-Dimensional; D020869:Gene Expression Profiling; D015964:Gene Expression Regulation, Bacterial; D006801:Humans; D007533:Isoleucine-tRNA Ligase / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D013058:Mass Spectrometry; D008826:Microbial Sensitivity Tests / Q000379:methods; D016712:Mupirocin / Q000494:pharmacology*; D020411:Oligonucleotide Array Sequence Analysis; D013203:Staphylococcal Infections / Q000382:microbiology; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000235:genetics / Q000254:growth & development / Q000378:metabolism; D059467:Transcriptome; D014774:Virulence / Q000187:drug effects
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D016712:Mupirocin; D007533:Isoleucine-tRNA Ligase