Diverse modulation of spa transcription by cell wall active antibiotics in Staphylococcus aureus

被引：16

作者：

Nielsen L.N. ^{[1
]}

Roggenbuck M. ^{[1
]}

Haaber J. ^{[1
]}

Ifrah D. ^{[1
]}

Ingmer H. ^{[1
]}

机构：

[1] Department of Veterinary Disease Biology, University of Copenhagen, Copenhagen

来源：

BMC Research Notes | / 5卷 / 1期

关键词：

Antibiotics; Biofilm formation; Protein A (spa); Staphylococcus aureus; Subinhibitory concentrations; Virulence;

D O I：

10.1186/1756-0500-5-457

中图分类号：

学科分类号：

摘要：

Abstract. Background: The aim of this study was to investigate the effect of various classes of clinically relevant antibiotics at sub-lethal concentrations on virulence gene expression and biofilm formation in Staphylococcus aureus. Findings. LacZ promoter fusions of genes related to staphylococcal virulence were used to monitor the effects of antibiotics on gene expression in a disc diffusion assay. The selected genes were hla and spa encoding -hemolysin and Protein A, respectively and RNAIII, the effector molecule of the agr quorum sensing system. The results were confirmed by quantitative real-time PCR. Additionally, we monitored the effect of subinhibitory concentrations of antibiotics on the ability of S. aureus to form biofilm in a microtiter plate assay. The results show that sub-lethal antibiotic concentrations diversely modulate expression of RNAIII, hla and spa. Consistently, expression of all three genes were repressed by aminoglycosides and induced by fluoroquinolones and penicillins. In contrast, the -lactam sub-group cephalosporins enhanced expression of RNAIII and hla but diversely affected expression of spa. The compounds cefalotin, cefamandole, cefoxitin, ceftazidime and cefixine were found to up-regulate spa, while down-regulation was observed for cefuroxime, cefotaxime and cefepime. Interestingly, biofilm assays demonstrated that the spa-inducing cefalotin resulted in less biofilm formation compared to the spa-repressing cefotaxime. Conclusions: We find that independently of the cephalosporin generation, cephalosporins oppositely regulate spa expression and biofilm formation. Repression of spa expression correlates with the presence of a distinct methyloxime group while induction correlates with an acidic substituted oxime group. As cephalosporines target the cell wall penicillin binding proteins we speculate that subtle differences in this interaction fine-tunes spa expression independently of agr. © 2012 Nielsen et al.; licensee BioMed Central Ltd.

引用

共 35 条

[1]

Davies J., Everything depends on everything else, Clin Microbiol Infect, 15, SUPPL. 1, pp. 1-4, (2009)

[2]

Kummerer K., The presence of pharmaceuticals in the environment due to human use-present knowledge and future challenges, J Environ Manage, 90, pp. 2354-2366, (2009)

[3]

Goh E.B., Yim G., Tsui W., McClure J., Surette M.G., Davies J., Transcriptional modulation of bacterial gene expression by subinhibitory concentrations of antibiotics, Proc Natl Acad Sci U S A, 99, pp. 17025-17030, (2002)

[4]

Ohlsen K., Ziebuhr W., Koller K.P., Hell W., Wichelhaus T.A., Hacker J., Effects of subinhibitory concentrations of antibiotics on alpha-toxin (hla) gene expression of methicillin-sensitive and methicillin-resistant Staphylococcus aureus isolates, Antimicrob Agents Chemother, 42, pp. 2817-2823, (1998)

[5]

Walsh C., Molecular mechanisms that confer antibacterial drug resistance, Nature, 406, pp. 775-781, (2000)

[6]

Lowy F.D., Staphylococcus aureus infections, N Engl J Med, 339, pp. 520-532, (1998)

[7]

Otto M., Staphylococcal biofilms, Curr Top Microbiol Immunol, 322, pp. 207-228, (2008)

[8]

Bhakdi S., Tranum-Jensen J., Alpha-toxin of Staphylococcus aureus, Microbiol Rev, 55, pp. 733-751, (1991)

[9]

Walev I., Martin E., Jonas D., Mohamadzadeh M., Muller-Klieser W., Kunz L., Bhakdi S., Staphylococcal alpha-toxin kills human keratinocytes by permeabilizing the plasma membrane for monovalent ions, Infect Immun, 61, pp. 4972-4979, (1993)

[10]

Gomez M.I., Lee A., Reddy B., Muir A., Soong G., Pitt A., Cheung A., Prince A., Staphylococcus aureus protein A induces airway epithelial inflammatory responses by activating TNFR1, Nat. Med., 10, pp. 842-848, (2004)

← 1 2 3 4 →