| Title | Genetic Diversity of Polymyxin-Resistance Mechanisms in Clinical Isolates of Carbapenem-Resistant Klebsiella pneumoniae: a Multicenter Study in China |
| Authors | Li, Ziyao Liu, Xinmeng Lei, Zichen Li, Chen Zhang, Feilong Wu, Yongli Yang, Xinrui Zhao, Jiankang Zhang, Yulin Hu, Yanning Shen, Fangfang Wang, Pingbang Yang, Junwen Liu, Yulei Lu, Binghuai |
| Affiliation | China Japan Friendship Inst Clin Med Sci, Beijing, Peoples R China China Japan Friendship Hosp, Ctr Resp Med, Natl Clin Res Ctr Resp Dis, Natl Ctr Resp Med,Lab Clin Microbiol & Infect Dis,, Beijing, Peoples R China Chinese Acad Med Sci, Inst Resp Med, Beijing, Peoples R China Chinese Acad Med Sci, Peking Union Med Coll, Beijing, Peoples R China Peking Univ China, Japan Friendship Sch Clin Med, Beijing, Peoples R China Liuyang Tradit Chinese Med Hosp, Changsha, Hunan, Peoples R China Changzhi Med Coll, Heping Hosp, Changzhi, Shanxi, Peoples R China Peoples Hosp Liuyang, Changsha, Hunan, Peoples R China Zhengzhou Univ, Dept Lab Med, Zhengzhou Key Lab Childrens Infect & Immun, Childrens Hosp, Zhengzhou, Henan, Peoples R China Beijing Anzhen Hosp, Dept Lab Med, Beijing, Peoples R China |
| Keywords | CHROMOSOMAL BETA-LACTAMASE COLISTIN PLASMIDS ENTEROBACTERALES HENAN |
| Issue Date | Feb-2023 |
| Publisher | MICROBIOLOGY SPECTRUM |
| Abstract | Polymyxin-resistant CRKP is a serious public health threat whose resistance mechanisms should be under continuous surveillance. Here, we collected 662 nonduplicate CRKP strains across China to identify the carbapenemase and polymyxin resistance genes and epidemiological features. Polymyxin has been the last resort to treat multidrug-resistant Klebsiella pneumonia. However, recent studies have revealed that polymyxin-resistant carbapenem-resistant Klebsiella pneumonia (PR-CRKP) emerged due to the mutations in chromosomal genes or the plasmid-harboring mcr gene, leading to lipopolysaccharide modification or efflux of polymyxin through pumps. Further surveillance was required. In the present study we collected PR-CRKP strains from 8 hospitals in 6 provinces/cities across China to identify the carbapenemase and polymyxin resistance genes and epidemiological features by whole-genome sequencing (WGS). The broth microdilution method (BMD) was performed to determine the MIC of polymyxin. Of 662 nonduplicate CRKP strains, 15.26% (101/662) were defined as PR-CRKP; 10 (9.90%) were confirmed as Klebsiella quasipneumoniae by WGS. The strains were further classified into 21 individual sequence types (STs) by using multilocus sequence typing (MLST), with ST11 being prevalent (68/101, 67.33%). Five carbapenemase types were identified among 92 CR-PRKP, bla(KPC-2) (66.67%), bla(NDM-1) (16.83%), bla(NDM-5) (0.99%), bla(IMP-4) (4.95%), and bla(IMP-38) (0.99%). Notably, 2 PR-CRKP strains harbored both bla(KPC-2) and bla(NDM-1). The inactivation of mgrB, associated significantly with high-level polymyxin resistance, was mainly caused by the insertion sequence (IS) insertion (62.96%, 17/27). Furthermore, acrR was inserted coincidently by ISkpn26 (67/101, 66.33%). The deletion or splicing mutations of crrCAB were significantly associated with ST11 and KL47 (capsule locus types), and diverse mutations of the ramR gene were identified. Only one strain carried the mcr gene. In summary, the high IS-inserted mgrB inactivation, the close relationship between ST11 and the deletion or splicing mutations of the crrCAB, and the specific features of PR-K. quasipneumoniae constituted notable features of our PR-CRKP strains in China.IMPORTANCE Polymyxin-resistant CRKP is a serious public health threat whose resistance mechanisms should be under continuous surveillance. Here, we collected 662 nonduplicate CRKP strains across China to identify the carbapenemase and polymyxin resistance genes and epidemiological features. Polymyxin resistance mechanism in 101 PR-CRKP strains in China were also investigated, 9.8% of which (10/101) were K. quasipneumoniae, as determined via WGS, and inactivation of mgrB remained the most crucial polymyxin resistance mechanism, significantly related to high-level resistance. Deletion or splicing mutations of crrCAB were significantly associated with ST11 and KL47. Diverse mutations of the ramR gene were identified. The plasmid complementation experiment and mRNA expression analysis further confirmed that the mgrB promoter and ramR played a critical role in polymyxin resistance. This multicenter study contributed to the understanding of antibiotic resistance forms in China. |
| URI | http://hdl.handle.net/20.500.11897/672166 |
| ISSN | 2165-0497 |
| DOI | 10.1128/spectrum.05231-22 |
| Indexed | SCI(E) |
| Appears in Collections: | 待认领 |
