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Compensatory mutations in agrC partly restore fitness in vitro to peptide deformylase inhibitor-resistant Staphylococcus aureus
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
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2012 (English)In: Journal of Antimicrobial Chemotherapy, ISSN 0305-7453, E-ISSN 1460-2091, Vol. 67, no 8, 1835-1842 p.Article in journal (Refereed) Published
Abstract [en]


To determine how the fitness cost of deformylase inhibitor resistance conferred by fmt mutations can be genetically compensated.


Resistant mutants were isolated and characterized with regard to their growth rates in vitro and in neutropenic mice, MIC and DNA sequence. Faster-growing compensated mutants were isolated by serial passage in culture medium, and for a subset of the resistant and compensated mutants whole-genome sequencing was performed.


Staphylococcus aureus mutants resistant to the peptide deformylase inhibitor actinonin had mutations in the fmt gene that conferred high-level actinonin resistance and reduced bacterial growth rate. Compensated mutants that remained fully resistant to actinonin and showed increased growth rates appeared within 30-60 generations of growth. Whole-genome sequencing and localized DNA sequencing of mutated candidate genes showed that alterations in the gene agrC were present in the majority of compensated strains. Resistant and compensated mutants grew at similar rates as the wild-type in a mouse thigh infection model.


Resistance to deformylase inhibitors due to fmt mutations reduces bacterial growth rates, but these costs can be reduced by mutations in the agrC gene. Mutants defective in fmt (with or without compensatory agrC mutations) grew well in an animal model, implying that they can also cause infection in a host.

Place, publisher, year, edition, pages
2012. Vol. 67, no 8, 1835-1842 p.
National Category
Infectious Medicine Microbiology in the medical area
URN: urn:nbn:se:uu:diva-194443DOI: 10.1093/jac/dks168ISI: 000306366000005PubMedID: 22577101OAI: oai:DiVA.org:uu-194443DiVA: diva2:605482
Available from: 2013-02-14 Created: 2013-02-14 Last updated: 2015-07-24Bibliographically approved

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Zorzet, AnnaAndersson, Dan I
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