TY - JOUR
T1 - Distribution and spread of the mobilised RND efflux pump gene cluster tmexCD-toprJ in clinical Gram-negative bacteria: a molecular epidemiological study
AU - Dong, Ning
AU - Zeng, Yu
AU - Wang, Yao
AU - Liu, Congcong
AU - Lu, Jiayue
AU - Cai, Chang
AU - Liu, Xue
AU - Chen, Yongkui
AU - Wu, Yongning
AU - Fang, Yinfei
AU - Fu, Yulin
AU - Hu, Yanyan
AU - Zhou, Hongwei
AU - Cai, Jiachang
AU - Hu, Fupin
AU - Wang, Shaolin
AU - Wang, Yang
AU - Wu, Yongning
AU - Chen, Gongxiang
AU - Shen, Zhangqi
AU - Chen, Sheng
AU - Zhang, Rong
N1 - Funding Information:
We would like to thank Jingren Zhang (Tsinghua University, Beijing, China) and Xueting Huang (Tsinghua University, Beijing, China) for their technical support. This work was supported by the National Natural Science Foundation of China (81861138052, 22193064, 81871705, 32225048, 82072341 and 2018YFD0500300, and 31930110), Guangdong Major Project of Basic and Applied Basic Research (2020B0301030005), and the Natural Science Foundation of Jiangsu Province (BK20220493).
Funding Information:
We would like to thank Jingren Zhang (Tsinghua University, Beijing, China) and Xueting Huang (Tsinghua University, Beijing, China) for their technical support. This work was supported by the National Natural Science Foundation of China (81861138052, 22193064, 81871705, 32225048, 82072341 and 2018YFD0500300, and 31930110), Guangdong Major Project of Basic and Applied Basic Research (2020B0301030005), and the Natural Science Foundation of Jiangsu Province (BK20220493).
Publisher Copyright:
© 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND license
PY - 2022/11
Y1 - 2022/11
N2 - Background: TMexCD1-TOprJ1, which is associated with phenotypic resistance to multiple classes of antibiotics, is a transmissible resistance-nodulation-division (RND) family efflux pump. However, the prevalence and genomic and phenotypic characteristics of clinical isolates with this important resistance determinant are poorly understood. In this study, we aimed to survey tmexCD-toprJ among clinical Gram-negative isolates collected from hospitals in China between 1991 and 2020 and characterise tmexCD-toprJ-positive clinical isolates. Methods: We conducted online data retrieval and active nationwide surveillance in China to screen tmexCD-toprJ-positive strains. We characterised tmexCD-toprJ-positive clinical strains for their antimicrobial susceptibility, genetic and functional characteristics, and the potential inter-species transmission route of tmexCD-toprJ with whole genome sequencing and bioinformatics analyses. The function of tmexCD-toprJ in Pseudomonas sp and Proteus sp was investigated by tmexD gene knockdown using an isopropylthio-β-galactoside-inducible CRISPR interference system. Findings: Data retrieval obtained 53 strains carrying tmexCD-toprJ, comprising 32 Pseudomonas spp, 11 Klebsiella pneumoniae, one Aeromonas spp, one Citrobacter freundii, and one uncultured bacterium from diverse niches. 48 (0·64%) of 7517 clinical isolates from China, including seven Klebsiella spp, one Proteus mirabilis, and 40 Pseudomonas spp, carried tmexCD-toprJ. These isolates exhibited multidrug resistance phenotypes and co-harboured resistance genes, such as mcr and carbapenemases genes. tmexCD-toprJ was encoded on both plasmids and chromosomes in all Klebsiella spp that carried plasmid-borne tmexCD-toprJ (n=7), P mirabilis carried chromosome-borne tmexCD-toprJ, and Pseudomonas spp carried either plasmid-borne (n=19) or chromosome-borne (n=21) ones. tmexCD-toprJ had undergone clonal and horizontal transmission among clinical pathogens. Eight different types of genetic context of tmexCD-toprJ were identified, each of which was associated with different mobile elements, including IntI, IS6100, TnAs1-like, ISRor5, ISVsa3, ISCfr-like, Tn5393, and IS222-like, which might facilitate its transmission. Knockdown of tmexD led to a four times decrease in tigecycline minimum inhibitory concentrations in both Pseudomonas spp and Proteus spp. Interpretation: Our study provides evidence to suggest that tmexCD-toprJ contributes to the antimicrobial resistance phenotypes in different bacterial species. tmexCD-toprJ has disseminated among diverse species of clinical pathogens, which warrants timely monitoring in clinical pathogens.
AB - Background: TMexCD1-TOprJ1, which is associated with phenotypic resistance to multiple classes of antibiotics, is a transmissible resistance-nodulation-division (RND) family efflux pump. However, the prevalence and genomic and phenotypic characteristics of clinical isolates with this important resistance determinant are poorly understood. In this study, we aimed to survey tmexCD-toprJ among clinical Gram-negative isolates collected from hospitals in China between 1991 and 2020 and characterise tmexCD-toprJ-positive clinical isolates. Methods: We conducted online data retrieval and active nationwide surveillance in China to screen tmexCD-toprJ-positive strains. We characterised tmexCD-toprJ-positive clinical strains for their antimicrobial susceptibility, genetic and functional characteristics, and the potential inter-species transmission route of tmexCD-toprJ with whole genome sequencing and bioinformatics analyses. The function of tmexCD-toprJ in Pseudomonas sp and Proteus sp was investigated by tmexD gene knockdown using an isopropylthio-β-galactoside-inducible CRISPR interference system. Findings: Data retrieval obtained 53 strains carrying tmexCD-toprJ, comprising 32 Pseudomonas spp, 11 Klebsiella pneumoniae, one Aeromonas spp, one Citrobacter freundii, and one uncultured bacterium from diverse niches. 48 (0·64%) of 7517 clinical isolates from China, including seven Klebsiella spp, one Proteus mirabilis, and 40 Pseudomonas spp, carried tmexCD-toprJ. These isolates exhibited multidrug resistance phenotypes and co-harboured resistance genes, such as mcr and carbapenemases genes. tmexCD-toprJ was encoded on both plasmids and chromosomes in all Klebsiella spp that carried plasmid-borne tmexCD-toprJ (n=7), P mirabilis carried chromosome-borne tmexCD-toprJ, and Pseudomonas spp carried either plasmid-borne (n=19) or chromosome-borne (n=21) ones. tmexCD-toprJ had undergone clonal and horizontal transmission among clinical pathogens. Eight different types of genetic context of tmexCD-toprJ were identified, each of which was associated with different mobile elements, including IntI, IS6100, TnAs1-like, ISRor5, ISVsa3, ISCfr-like, Tn5393, and IS222-like, which might facilitate its transmission. Knockdown of tmexD led to a four times decrease in tigecycline minimum inhibitory concentrations in both Pseudomonas spp and Proteus spp. Interpretation: Our study provides evidence to suggest that tmexCD-toprJ contributes to the antimicrobial resistance phenotypes in different bacterial species. tmexCD-toprJ has disseminated among diverse species of clinical pathogens, which warrants timely monitoring in clinical pathogens.
UR - http://www.scopus.com/inward/record.url?scp=85142420237&partnerID=8YFLogxK
U2 - 10.1016/S2666-5247(22)00221-X
DO - 10.1016/S2666-5247(22)00221-X
M3 - Journal article
AN - SCOPUS:85142420237
SN - 2666-5247
VL - 3
SP - e846-e856
JO - The Lancet Microbe
JF - The Lancet Microbe
IS - 11
ER -