Please use this identifier to cite or link to this item: http://ahro.austin.org.au/austinjspui/handle/1/11782
Title: Analysis of the small RNA transcriptional response in multidrug-resistant Staphylococcus aureus after antimicrobial exposure.
Authors: Howden, Benjamin P;Beaume, Marie;Harrison, Paul F;Hernandez, David;Schrenzel, Jacques;Seemann, Torsten;Francois, Patrice;Stinear, Timothy P
Affiliation: Austin Centre for Infection Research, Infectious Diseases Department, Austin Health, Heidelberg, Victoria, Australia. Benjamin.Howden@austin.org.au
Issue Date: 3-Jun-2013
Citation: Antimicrobial Agents and Chemotherapy 2013; 57(8): 3864-74
Abstract: The critical role of noncoding small RNAs (sRNAs) in the bacterial response to changing conditions is increasingly recognized. However, a specific role for sRNAs during antibiotic exposure has not been investigated in Staphylococcus aureus. Here, we used Illumina RNA-Seq to examine the sRNA response of multiresistant sequence type 239 (ST239) S. aureus after exposure to four antibiotics (vancomycin, linezolid, ceftobiprole, and tigecycline) representing the major classes of antimicrobials used to treat methicillin-resistant S. aureus (MRSA) infections. We identified 409 potential sRNAs and then compared global sRNA and mRNA expression profiles at 2 and 6 h, without antibiotic exposure and after exposure to each antibiotic, for a vancomycin-susceptible strain (JKD6009) and a vancomycin-intermediate strain (JKD6008). Exploration of this data set by multivariate analysis using a novel implementation of nonnegative matrix factorization (NMF) revealed very different responses for mRNA and sRNA. Where mRNA responses clustered with strain or growth phase conditions, the sRNA responses were predominantly linked to antibiotic exposure, including sRNA responses that were specific for particular antibiotics. A remarkable feature of the antimicrobial response was the prominence of antisense sRNAs to genes encoding proteins involved in protein synthesis and ribosomal function. This study has defined a large sRNA repertoire in epidemic ST239 MRSA and shown for the first time that a subset of sRNAs are part of a coordinated transcriptional response to specific antimicrobial exposures in S. aureus. These data provide a framework for interrogating the role of staphylococcal sRNAs in antimicrobial resistance and exploring new avenues for sRNA-based antimicrobial therapies.
Internal ID Number: 23733475
URI: http://ahro.austin.org.au/austinjspui/handle/1/11782
DOI: 10.1128/AAC.00263-13
URL: http://www.ncbi.nlm.nih.gov/pubmed/23733475
Type: Journal Article
Subjects: Acetamides.pharmacology
Anti-Bacterial Agents.pharmacology
Cephalosporins.pharmacology
Methicillin-Resistant Staphylococcus aureus.drug effects.genetics.metabolism
Microbial Sensitivity Tests
Minocycline.analogs & derivatives.pharmacology
Oxazolidinones.pharmacology
Protein Biosynthesis
RNA, Bacterial.genetics.metabolism
RNA, Messenger.genetics.metabolism
RNA, Small Untranslated.genetics.metabolism
Sequence Analysis, RNA
Transcription, Genetic
Vancomycin.pharmacology
Appears in Collections:Journal articles

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