RNA-based antibiotic susceptibility testing of tmexCD-toprJ-mediated tigecycline resistance in Klebsiella pneumoniae  

作　　者：Feiyu Yu Haijie Zhang Shuyao Zhu Zhiqiang Wang Yuan Liu 

机构地区：[1]Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses,College of Veterinary Medicine,Yangzhou University,Yangzhou 225009,China [2]Joint International Research Laboratory of Agriculture and Agri-Product Safety,the Ministry of Education of China,Yangzhou University,Yangzhou 225009,China [3]Institute of Comparative Medicine,Yangzhou University,Yangzhou 225009,China

出　　处：《One Health Advances》2023年第1期106-116,共11页全健康进展（英文）

基　　金：supported by the National Key Research and Development Program of China(2021YFD1801000);National Natural Science Foundation of China(32222084,32002331 and 32172907);Jiangsu Agricultural Science and Technology Innovation Fund(CX(21)2010);A Project Funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions(PAPD)and 111 Project D18007。

摘　　要：The emergence and prevalence of plasmid-encoded RND-type efflux pump TMexCD-TOprJ severely compromise tigecycline treatment,which is recognized as the last resort for multidrug-resistant(MDR)Gram-negative bacterial infections.There is an urgent need for rapid antibiotic susceptibility testing(AST)that can simultaneously identify the genotype and phenotype of tmexCD-toprJ-positive bacteria.Through characterizing transcriptional profiling responses of tmexCD-toprJ-positive and-negative strains after exposure to 2μg/mL tigecycline,here we identified 12 differentially RNA biomarkers and developed an RNA-based AST(RBAST)to distinguish tmexCD-toprJ-positive and-negative K.pneumoniae.These mRNA biomarkers were successfully validated in tigecycline exposure time variations,concentration shifts,and other tmexCD-toprJ variants.In addition,a group of clinical isolated strains was effectively distinguished using RBAST,with an accuracy of over 94%during 3 h test period.Our work highlights the potential of RNA transcripts as biomarkers for rapid AST,which will contribute to deploying effective antibiotic regimens in clinical practice.

关 键 词：Antibiotic resistance tmexCD-toprJ TIGECYCLINE AST Bacteria 

分 类 号：R96[医药卫生—药理学] R563.1[医药卫生—药学]