To the Editor:Klebsiella pneumoniae(K.pneumoniae)is a common opportunistic pathogen with rising prevalence in clinical settings.A multicenter study reported its detection rate among hospitalized adults with community-...To the Editor:Klebsiella pneumoniae(K.pneumoniae)is a common opportunistic pathogen with rising prevalence in clinical settings.A multicenter study reported its detection rate among hospitalized adults with community-acquired pneumonia(CAP)has increased annually,making it the leading cause of severe CAP(SCAP),surpassing Streptococcus pneumoniae.[1]Hypervirulent K.pneumoniae(hvKP),especially sequence type(ST)23,[2]exhibits enhanced virulence and colonization,driven by multiple siderophore systems and virulence plasmids,and is linked to high mortality.[3]Alarmingly,tigecycline resistance in ST23 strains is increasing.While tigecycline is crucial for treating multidrug-resistant and carbapenem-resistant K.pneumoniae,resistance—mainly due to efflux pump overexpression,enzymatic inactivation,and target site mutations—has been widely reported.[4]Mutations in regulators such as RamR(a TetR-family transcriptional repressor regulating ramA)are involved,[5]but their roles in hvKP remain unclear.In this study,a novel RamR point mutation was identified and validated via whole-genome sequencing,gene editing,quantitative real-time polymerase chain reaction(qRT-PCR),proteomics,and electrophoretic mobility shift assay(EMSA).This mutation reduced ramA repression,resulting in efflux pump overexpression,and conferred tigecycline resistance.The Medical Ethics Committee of Qingdao Municipal Hospital approved this study(No.XM:2023-030).展开更多
基金supported by grants from the National Key Research and Development Program of China(No.2022YFE0199800)Qingdao Science and Technology Wellness Promotion Demonstration Program(No.24-1-8-smjk-13-nsh)+4 种基金the National Natural Science Foundation of China(No.82271658)the SKLMT Frontiers and Challenges Project(No.SKLMTFCP-2023-01)the Shandong Provincial Natural Science Foundation(Nos.ZR2024QD228 and ZR2024QC311)the Qingdao Natural Science Foundation(No.24-4-4-zrjj-40-jch)the Opening Project of the Shanghai Key Laboratory of Atmospheric Particle Pollution and Prevention(LAP)(No.FDLAP24008).
文摘To the Editor:Klebsiella pneumoniae(K.pneumoniae)is a common opportunistic pathogen with rising prevalence in clinical settings.A multicenter study reported its detection rate among hospitalized adults with community-acquired pneumonia(CAP)has increased annually,making it the leading cause of severe CAP(SCAP),surpassing Streptococcus pneumoniae.[1]Hypervirulent K.pneumoniae(hvKP),especially sequence type(ST)23,[2]exhibits enhanced virulence and colonization,driven by multiple siderophore systems and virulence plasmids,and is linked to high mortality.[3]Alarmingly,tigecycline resistance in ST23 strains is increasing.While tigecycline is crucial for treating multidrug-resistant and carbapenem-resistant K.pneumoniae,resistance—mainly due to efflux pump overexpression,enzymatic inactivation,and target site mutations—has been widely reported.[4]Mutations in regulators such as RamR(a TetR-family transcriptional repressor regulating ramA)are involved,[5]but their roles in hvKP remain unclear.In this study,a novel RamR point mutation was identified and validated via whole-genome sequencing,gene editing,quantitative real-time polymerase chain reaction(qRT-PCR),proteomics,and electrophoretic mobility shift assay(EMSA).This mutation reduced ramA repression,resulting in efflux pump overexpression,and conferred tigecycline resistance.The Medical Ethics Committee of Qingdao Municipal Hospital approved this study(No.XM:2023-030).
