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 in...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.展开更多
基金supported by the National Key Research and Development Program of China(2021YFD1801000)National Natural Science Foundation of China(32222084,32002331 and 32172907)+1 种基金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。
文摘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.
