Effects of sub-lethal concentrations of mupirocin on global transcription in Staphylococcus aureus 8325-4 and a model for escape from inhibition

Alhoufie, STS; Foster, HA

Abstract

Staphylococcus aureus is a major pathogen in both hospital and community settings causing infections ranging from mild skin and wound infections to life-threatening systemic illness. Gene expression changes due to the stringent response have been studied in Staphylococcus aureus using lethal concentrations of mupirocin but no studies have investigated the effects of sub-lethal concentrations. S. aureus 8325-4
was exposed to sub-inhibitory concentrations of mupirocin. The production of ppGpp was determined via HPLC and the effects on global transcription were studied by
RNAseq analysis. Growth inhibition had occurred after 1 h of treatment and metabolic
analysis revealed that the stringent response alarmone ppGpp was detected and GTP
concentrations decreased. Transcriptome profiles showed that global transcriptional
alterations were similar to those for S. aureus after treatment with lethal concentrations
of mupirocin including the repression of genes involved in transcription, translation and replication machineries. Furthermore, up-regulation for genes involved in stress responses, amino acid biosynthesis and transport as well as for some virulence factor
genes was observed. However, ppGpp was not detectable after 12 or 24 h and cell growth had resumed although some transcriptional changes remained. Sub-lethal
concentrations of mupirocin induce the stringent response but cells adapt and resume growth once ppGpp levels decrease.

Citation

Alhoufie, S., & Foster, H. (2016). Effects of sub-lethal concentrations of mupirocin on global transcription in Staphylococcus aureus 8325-4 and a model for escape from inhibition. Journal of Medical Microbiology, 65, https://doi.org/10.1099/jmm.0.000270

• Journal Article Type: Article
• Acceptance Date: May 6, 2016
• Online Publication Date: May 16, 2016
• Publication Date: May 16, 2016
• Deposit Date: Jun 14, 2016
• Publicly Available Date: May 18, 2017
• Journal: Journal of Medical Microbiology
• Print ISSN: 0022-2615
• Electronic ISSN: 1473-5644
• Publisher: Microbiology Society
• Volume: 65
• DOI: https://doi.org/10.1099/jmm.0.000270
• Publisher URL: http://dx.doi.org/10.1099/jmm.0.000270
• Related Public URLs: http://jmm.microbiologyresearch.org/content/journal/jmm