The Ribosomal S10 Protein Is a General Target for Decreased Tigecycline Susceptibility

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dc.citation.firstpage5561en_US
dc.citation.issueNumber9en_US
dc.citation.journalTitleAntimicrobial Agents and Chemotherapyen_US
dc.citation.lastpage5566en_US
dc.citation.volumeNumber59en_US
dc.contributor.authorBeabout, Kathrynen_US
dc.contributor.authorHammerstrom, Troy G.en_US
dc.contributor.authorPerez, Anisha Mariaen_US
dc.contributor.authorMagalhães, Bárbara de Freitasen_US
dc.contributor.authorPrater, Amy G.en_US
dc.contributor.authorClements, Thomas P.en_US
dc.contributor.authorArias, Cesar A.en_US
dc.contributor.authorSaxer, Gerdaen_US
dc.contributor.authorShamoo, Yousifen_US
dc.date.accessioned2015-09-24T18:13:01Zen_US
dc.date.available2015-09-24T18:13:01Zen_US
dc.date.issued2015en_US
dc.description.abstractTigecycline is a translational inhibitor with efficacy against a wide range of pathogens. Using experimental evolution, we adapted Acinetobacter baumannii, Enterococcus faecium, Escherichia coli, and Staphylococcus aureus to growth in elevated tigecycline concentrations. At the end of adaptation, 35 out of 47 replicate populations had clones with a mutation in rpsJ, the gene that encodes the ribosomal S10 protein. To validate the role of mutations in rpsJ in conferring tigecycline resistance, we showed that mutation of rpsJ alone in Enterococcus faecalis was sufficient to increase the tigecycline MIC to the clinical breakpoint of 0.5 μg/ml. Importantly, we also report the first identification of rpsJ mutations associated with decreased tigecycline susceptibility in A. baumannii, E. coli, and S. aureus. The identified S10 mutations across both Gram-positive and -negative species cluster in the vertex of an extended loop that is located near the tigecycline-binding pocket within the 16S rRNA. These data indicate that S10 is a general target of tigecycline adaptation and a relevant marker for detecting reduced susceptibility in both Gram-positive and -negative pathogens.en_US
dc.identifier.citationBeabout, Kathryn, Hammerstrom, Troy G., Perez, Anisha Maria, et al.. "The Ribosomal S10 Protein Is a General Target for Decreased Tigecycline Susceptibility." <i>Antimicrobial Agents and Chemotherapy,</i> 59, no. 9 (2015) American Society for Microbiology: 5561-5566. http://dx.doi.org/10.1128/AAC.00547-15.en_US
dc.identifier.doihttp://dx.doi.org/10.1128/AAC.00547-15en_US
dc.identifier.urihttps://hdl.handle.net/1911/81714en_US
dc.language.isoengen_US
dc.publisherAmerican Society for Microbiologyen_US
dc.rightsThis is an author's peer-reviewed final manuscript, as accepted by the publisher. The published article is copyrighted by the American Society of Microbiology.en_US
dc.titleThe Ribosomal S10 Protein Is a General Target for Decreased Tigecycline Susceptibilityen_US
dc.typeJournal articleen_US
dc.type.dcmiTexten_US
dc.type.publicationpost-printen_US
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