OBJECTIVES: 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.
OBJECTIVES: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.
Authors: Emma Falck; Jari T Hautala; Mikko Karttunen; Paavo K J Kinnunen; Michael Patra; Heikki Saaren-Seppälä; Ilpo Vattulainen; Susanne K Wiedmer; Juha M Holopainen Journal: Biophys J Date: 2006-06-16 Impact factor: 4.033
Authors: Kelsi L Anderson; Corbette Roberts; Terrence Disz; Veronika Vonstein; Kaitlyn Hwang; Ross Overbeek; Patrick D Olson; Steven J Projan; Paul M Dunman Journal: J Bacteriol Date: 2006-10 Impact factor: 3.490
Authors: Fionnuala McAleese; Shang Wei Wu; Krzysztof Sieradzki; Paul Dunman; Ellen Murphy; Steven Projan; Alexander Tomasz Journal: J Bacteriol Date: 2006-02 Impact factor: 3.490
Authors: Jessica O O'Leary; Mark J Langevin; Christopher T D Price; Jon S Blevins; Mark S Smeltzer; John E Gustafson Journal: FEMS Microbiol Lett Date: 2004-08-15 Impact factor: 2.742
Authors: Malcolm J Horsburgh; Joanne L Aish; Ian J White; Les Shaw; James K Lithgow; Simon J Foster Journal: J Bacteriol Date: 2002-10 Impact factor: 3.490
Authors: Stacey L Kolar; Vijayaraj Nagarajan; Anna Oszmiana; Frances E Rivera; Halie K Miller; Jessica E Davenport; James T Riordan; Jan Potempa; David S Barber; Joanna Koziel; Mohamed O Elasri; Lindsey N Shaw Journal: Microbiology (Reading) Date: 2011-05-12 Impact factor: 2.777
Authors: Meredith A Benson; Sarit Lilo; Gregory A Wasserman; Matthew Thoendel; Amanda Smith; Alexander R Horswill; John Fraser; Richard P Novick; Bo Shopsin; Victor J Torres Journal: Mol Microbiol Date: 2011-06-16 Impact factor: 3.501
Authors: Jesus A Cuaron; Santosh Dulal; Yang Song; Atul K Singh; Cesar E Montelongo; Wanqin Yu; Vijayaraj Nagarajan; Radheshyam K Jayaswal; Brian J Wilkinson; John E Gustafson Journal: Phytother Res Date: 2012-05-23 Impact factor: 5.878
Authors: Hai-Bin Luo; Aleksandra A Knapik; Janusz J Petkowski; Matthew Demas; Igor A Shumilin; Heping Zheng; Maksymilian Chruszcz; Wladek Minor Journal: J Struct Funct Genomics Date: 2013-08-21
Authors: James T Riordan; JoAnne M Dupre; Stephanie A Cantore-Matyi; Atul Kumar-Singh; Yang Song; Shahrear Zaman; Sonia Horan; Nada S Helal; Vijayaraj Nagarajan; Mohamed O Elasri; Brian J Wilkinson; John E Gustafson Journal: Ann Clin Microbiol Antimicrob Date: 2011-07-21 Impact factor: 3.944