The fusidic acid stimulon of Staphylococcus aureus.
OBJECTIVE
Fusidic acid interferes with the release of elongation factor G (EF-G) after the translocation step of protein synthesis. The objective of this study was to characterize the fusidic acid stimulon of a fusidic acid-susceptible strain of Staphylococcus aureus (SH1000).


METHODS
S. aureus microarrays and real-time PCR determined transcriptome alterations occurring in SH1000 grown with fusidic acid. The Staphylococcus aureus microarray meta-database (SAMMD) compared and contrasted the SH1000 fusidic stimulon with 89 other S. aureus transcriptional datasets. Fusidic acid gradient analyses with mutant-parent strain pairs were used to identify genes required for intrinsic fusidic acid susceptibility identified during transcriptional analysis.


RESULTS
Many genes altered by fusidic acid challenge are associated with protein synthesis. SAMMD analysis determined that the fusidic acid stimulon has the greatest overlap with the S. aureus cold shock and stringent responses. Six out of nine peptidoglycan hydrolase genes making up the two component YycFG regulon were also up-regulated by fusidic acid, as were a carboxylesterase gene (est) and two putative drug efflux pump genes (emr-qac1 and macA). Genes down-regulated by fusidic acid induction encoded a putative secreted acid phosphatase and a number of protease genes. Roles for the agr operon, the peptidoglycan hydrolase gene isaA and two proteases (htrA1 and htrA2) in the expression of fusidic acid susceptibility were revealed.


CONCLUSIONS
The SH1000 fusidic acid stimulon includes genes involved with two stress responses, YycFG-regulated cell wall metabolism, drug efflux, and protein synthesis and turnover.
Delgado
Alejandro
A
Microbiology Group, Department of Biology, New Mexico State University, Las Cruces, NM 88003, USA.
Zaman
Shahrear
S
Muthaiyan
Arunachalam
A
Nagarajan
Vijayaraj
V
Elasri
Mohamed O
MO
Wilkinson
Brian J
BJ
Gustafson
John E
JE
D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D005672:Fusidic Acid / Q000494:pharmacology*; D020869:Gene Expression Profiling; D015964:Gene Expression Regulation, Bacterial; D005798:Genes, Bacterial; D020411:Oligonucleotide Array Sequence Analysis; D014176:Protein Biosynthesis / Q000187:drug effects; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000235:genetics
D000900:Anti-Bacterial Agents; D005672:Fusidic Acid
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