Emergence and dissemination of extensively drug-resistant ST307 Klebsiella pneumoniae in China
Source: PubMed Central Open Access, NCBI / U.S. National Library of Medicine
Abstract Carbapenem-resistant(CRKP) poses a significant threat to global public health. Identifying high-risk clones that facilitate the global dissemination of carbapenemases is essential for developing effective strategies to address this challenge. Here, we collected 29 ST307 CRKP isolates harbouring theand/orgenes from three hospitals.was carried by the IncX3 plasmid, andwas located on an IncFII plasmid. All of them were horizontally transmissible as verified by plasmid conjugation assays. Phylogenetic analysis revealed a clonal outbreak involving 27 of the isolates in this study and further demonstrated an emerging trend of- and-positive CRKP strains within the ST307 lineages in China since 2023. Resistance to ‘last-resort’ antibiotics mediated by genetic mutations is a major contributor to treatment failure in CRKP infections. In this study, we functionally confirmed that the plasmid-borne(A)mutation confers resistance to both tigecycline and eravacycline. The results of the murine bloodstream infection model further demonstrated that the(A)mutation increased the treatment cost of tigecycline. Furthermore, we found colistin resistance in ST307 CRKP primarily mediated by mutations in theandgenes. Specific mutation patterns, includingdisruption by IS,W20* andS203P substitutions, were identified in nine colistin-resistant ST307 CRKP isolates in this study. These findings highlight the need for enhanced surveillance and control measures to prevent the potential widespread o
Abstract
Abstract Carbapenem-resistant(CRKP) poses a significant threat to global public health. Identifying high-risk clones that facilitate the global dissemination of carbapenemases is essential for developing effective strategies to address this challenge. Here, we collected 29 ST307 CRKP isolates harbouring theand/orgenes from three hospitals.was carried by the IncX3 plasmid, andwas located on an IncFII plasmid. All of them were horizontally transmissible as verified by plasmid conjugation assays. Phylogenetic analysis revealed a clonal outbreak involving 27 of the isolates in this study and further demonstrated an emerging trend of- and-positive CRKP strains within the ST307 lineages in China since 2023. Resistance to ‘last-resort’ antibiotics mediated by genetic mutations is a major contributor to treatment failure in CRKP infections. In this study, we functionally confirmed that the plasmid-borne(A)mutation confers resistance to both tigecycline and eravacycline. The results of the murine bloodstream infection model further demonstrated that the(A)mutation increased the treatment cost of tigecycline. Furthermore, we found colistin resistance in ST307 CRKP primarily mediated by mutations in theandgenes. Specific mutation patterns, includingdisruption by IS,W20* andS203P substitutions, were identified in nine colistin-resistant ST307 CRKP isolates in this study. These findings highlight the need for enhanced surveillance and control measures to prevent the potential widespread outbreak of extensively drug-resistant ST307 isolates in China.