期刊
MICROBIOLOGY SPECTRUM
卷 9, 期 2, 页码 -出版社
AMER SOC MICROBIOLOGY
DOI: 10.1128/Spectrum.00648-21
关键词
antibiotic resistance; tet(X); tigecycline; antibiotic susceptibility determination; bacteria
类别
资金
- National Natural Science Foundation of China [32172907, 32002331]
- National Key Research and Development Program of China [2018YFA0903400]
- Natural Science Foundation of Jiangsu Province of China [BK20190893]
- Agricultural Science and Technology Independent Innovation Fund of Jiangsu Province [CX(20)3091, CX(21)2010]
- China Postdoctoral Science Foundation [2019M651984, 2021T140579]
- Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD)
- Young Elite Scientists Sponsorship Program by CAST [2020QNRC001]
The emergence of novel plasmid-mediated tigecycline resistance genes, such as tet(X), poses a serious threat to public health worldwide. A rapid and accurate RNA-based AST (RBAST) assay has been developed to effectively distinguish tet(X)-positive and -negative strains, with an assay time of 3 hours and 87.9% accuracy. This method may be useful for early antibiotic choices and combating antibiotic resistance.
The emergence and prevalence of novel plasmid-mediated tigecycline resistance genes, namely, tet(X) and their variants, pose a serious threat to public health worldwide. Rapid and accurate antibiotic susceptibility testing (AST) that can simultaneously detect the genotype and phenotype of tet(X)-positive bacteria may contribute to the deployment of an effective antibiotic arsenal, mortality reduction, and a decrease in the use of broad-spectrum antimicrobial agents. However, current bacterial growth-based AST methods, such as broth microdilution, are time consuming and delay the prompt treatment of infectious diseases. Here, we developed a rapid RNA-based AST (RBAST) assay to effectively distinguish tet(X)-positive and -negative strains. RBAST works by detecting specific mRNA expression signatures in bacteria after short-term tigecycline exposure. As a proof of concept, a panel of clinical isolates was characterized successfully by using the RBAST method, with a 3-h assay time and 87.9% accuracy (95% confidence interval [CI], 71.8% to 96.6%). Altogether, our findings suggest that RNA signatures upon antibiotic exposure are promising biomarkers for the development of rapid AST, which could inform early antibiotic choices. IMPORTANCE Infections caused by multidrug-resistant (MDR) Gram-negative pathogens are an increasing threat to global health. Tigecycline is one of the last-resort antibiotics for the treatment of these complicated infections; however, the emergence of plasmid-encoded tigecycline resistance genes, namely, tet(X), severely diminishes its clinical efficacy. Currently, there is a lack of rapid and accurate antibiotic susceptibility testing (AST) for the detection of tet(X)-positive bacteria. In this study, we developed a rapid and robust RNA-based antibiotic susceptibility determination (RBAST) assay to effectively distinguish tet(X)-negative and -positive strains using specific RNA biomarkers in bacteria after tigecycline exposure. Using this RBAST method, we successfully characterized a set of clinical strains in 3 h. Our data indicate that the RBAST assay is useful for identifying tet(X)-positive Escherichia coli.
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