Please use this identifier to cite or link to this item: http://ahro.austin.org.au/austinjspui/handle/1/11633
Title: The RpoB H₄₈₁Y rifampicin resistance mutation and an active stringent response reduce virulence and increase resistance to innate immune responses in Staphylococcus aureus.
Authors: Gao, Wei;Cameron, David R;Davies, John K;Kostoulias, Xenia;Stepnell, Justin;Tuck, Kellie L;Yeaman, Michael R;Peleg, Anton Y;Stinear, Timothy P;Howden, Benjamin P
Affiliation: Infectious Diseases Department, Austin Centre for Infection Research, University of Melbourne, Australia.
Issue Date: 18-Dec-2012
Citation: The Journal of Infectious Diseases 2012; 207(6): 929-39
Abstract: The occurrence of mutations in methicillin-resistant Staphylococcus aureus (MRSA) during persistent infection leads to antimicrobial resistance but may also impact host-pathogen interactions. Here, we investigate the host-pathogen consequences of 2 mutations arising in clinical MRSA during persistent infection: RpoB H₄₈₁Y, which is linked to rifampicin resistance, and RelA F₁₂₈Y, which is associated with an active stringent response. Allelic exchange experiments showed that both mutations cause global transcriptional changes, leading to upregulation of capsule production, with attenuated virulence in a murine bacteremia model and reduced susceptibility to both antimicrobial peptides and whole-blood killing. Disruption of capsule biosynthesis reversed these impacts on innate immune function. These data clearly link MRSA persistence and reduced virulence to the same mechanisms that alter antimicrobial susceptibility. Our study highlights the wider consequences of suboptimal antimicrobial use, where drug resistance and immune escape mechanisms coevolve, thus increasing the likelihood of treatment failure.
Internal ID Number: 23255563
URI: http://ahro.austin.org.au/austinjspui/handle/1/11633
DOI: 10.1093/infdis/jis772
URL: http://www.ncbi.nlm.nih.gov/pubmed/23255563
Type: Journal Article
Subjects: Animals
Bacterial Capsules.genetics.immunology.metabolism
DNA-Directed RNA Polymerases.genetics
Drug Resistance, Bacterial.genetics
Female
Host-Pathogen Interactions.genetics.immunology
Humans
Immunity, Innate
Methicillin-Resistant Staphylococcus aureus.drug effects.genetics.pathogenicity
Mice
Mice, Inbred BALB C
Phenotype
Polymorphism, Single Nucleotide
Rifampin
Staphylococcal Infections.immunology
Transcription Factor RelA.genetics
Transcription, Genetic.genetics
Up-Regulation
Virulence.genetics
alpha-Defensins.pharmacology
beta-Defensins.pharmacology
Appears in Collections:Journal articles

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