期刊
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
卷 59, 期 9, 页码 5561-5566出版社
AMER SOC MICROBIOLOGY
DOI: 10.1128/AAC.00547-15
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资金
- National Institute of Allergy and Infectious Diseases at the National Institutes of Health [R01 A1080714]
- Defense Threat Reduction Agency [HDTRA1010-0069]
- Keck Center of the Gulf Coast Consortia on the Houston Area Molecular Biophysics Training Program [NIGMS T32 GM008280]
- National Institute of Allergy and Infectious Diseases National Institutes of Health [R01A1093749]
Tigecycline 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 mu g/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.
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