Persistent ciprofloxacin exposure induced the transformation of Klebsiella pneumoniae small colony variant into mucous phenotype

作者全名："Zou, Hua; Li, Qian; Su, Yan; Zhang, Lei; Zhang, Xinyuan; Li, Chunli"

作者地址："[Zou, Hua; Li, Qian; Su, Yan; Zhang, Lei; Zhang, Xinyuan; Li, Chunli] Chongqing Med Univ, Women & Childrens Hosp, Chongqing Hlth Ctr Women & Children, Dept Lab Med, Chongqing, Peoples R China"

通信作者："Li, CL (通讯作者)，Chongqing Med Univ, Women & Childrens Hosp, Chongqing Hlth Ctr Women & Children, Dept Lab Med, Chongqing, Peoples R China."

来源：FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY

ESI学科分类：MICROBIOLOGY

WOS号：WOS:001095683900001

JCR分区：Q1

影响因子：4.6

年份：2023

卷号：13

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：small colony variant; Klebsiella pneumoniae; subinhibitory concentrations of antibiotics; Ciprofloxacin; umuC; IcmK

摘要："Introduction: Small colony variant (SCV) is a bacterial phenotype closely related to persistent and recurrent infections. SCVs are mutations that occur within bacterial populations, resulting in a change in bacterial morphology and the formation of small colonies. This morphological change may enhance bacterial resistance to antibiotics and contribute to persistent and recurrent infections.Methods: We isolated Klebsiella pneumoniae (KPN) and its SCV from a child with recurrent respiratory tract infections. KPN and SCV were treated with subinhibitory concentrations of antibiotics. growth curves, serum resistance experiments, macrophage phagocytosis experiments and whole genome sequencing were used to characterize KPN and SCV.Results: After treating KPN and SCV with subinhibitory concentrations of antibiotics, we found that ciprofloxacin induced the SCV transition to the mucoid phenotype. We found that the growth of mucoid Klebsiella pneumoniae was significantly slower than maternal strain and SCV though growth curves. Serum resistance experiments showed that mucoid strains had significantly higher serum resistance compared to maternal strain and SCV. Macrophage phagocytosis experiments revealed that SCV had significantly higher intracellular survival rates compared to maternal strain and mucoid strains. Differential gene analysis of three strains revealed that the mucoid strain contained DNA polymerase V subunit UmuC gene on the plasmid, while the SCV strain had an additional IcmK family IV secretion protein on its plasmid.Discussion: Our study showed the SCV of KPN changed to a mucoid colony when exposed to subinhibitory concentrations of ciprofloxacin. The higher resistance of serum of mucoid colonies was possibly related to the UmuC gene, while the increased intracellular survival of SCV may be related to the IcmK family type IV secretion proteins."

基金机构："The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This study was supported in part by the Health Bureau in Chongqing (Grant number, CSTB2022NSCQ-MSX0807). [CSTB2022NSCQ-MSX0807]; Health Bureau in Chongqing"

基金资助正文："The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This study was supported in part by the Health Bureau in Chongqing (Grant number, CSTB2022NSCQ-MSX0807)."