Project description:Genome-wide transcriptional profiling studies of the growth of bacteria with antimicrobial agents often reveals aspects of the drug-specific protective bacterial response. Fusidic acid is a steroid antimicrobial that inhibits protein synthesis by interfering with the release of elongation factor G (EF-G) after it has functioned in the translocation step. Two hundred and seventy two genes were both up- and down-regulated in a fusidic acid-susceptible strain of Staphylococcus aureus following challenge with 2 mg/L-1 fusidic acid for 15 min. Many genes altered by fusidic acid challenge are associated with protein synthesis such as fusA, which encodes EF-G which was up-regulated following exposure to the drug. The Staphylococcus microarray meta-database which curates and compares S. aureus transcriptome data revealed that the fusidic acid stimulon has the greatest overlap with the S. aureus cold shock- and stringent-responses. Six out of 9 autolysin genes making up the two component YycFG regulon (ssaA1-ssaA4, isaA and sceD) were also upregulated by fusidic acid; as were a carboxylesterase (est) and two putative Emr-Qac-like multidrug efflux pumps (emr-qac1 and emr-qac2). Genes down-regulated by fusidic acid induction encode a putative secreted acid phosphatase (sapS) and a number of protease genes (yjbG1, yjbG2, htrA1 and htrA2). Transcriptional analysis in conjunction with mutant fusidic acid susceptibility experiments revealed that th45 e virulence gene regulatory agr operon, a YycFG controlled peptidoglycan hydrolase gene isaA and the proteases htrA1 and htrA2 are required for the expression of wild-type levels of fusidic acid susceptibility.

2008-08-25 | GSE12210 | GEO

Reversing the Natural Drug Resistance of Gram-Negative Bacteria to Fusidic Acid via Forming Drug-Phospholipid Complex.

Project description: Not available

| S-EPMC10885999 | biostudies-literature

Drug interaction potential of high-dose rifampicin in patients with pulmonary tuberculosis.

Project description: Not available

| S-EPMC10583668 | biostudies-literature