"Emergence of a clinical <i>Salmonella enterica</i> serovar 1,4,[5], 12: i:-isolate, ST3606, in China with susceptibility decrease to ceftazidime-avibactam carrying a novel <i>bla</i>_CTX-M-261 variant and a <i>bla</i>_NDM-5"

作者全名："Wei, Jie; Shen, Shimei; Zhang, Qinghuan; Lu, Jinping; Mao, Shenglan; Zou, Chunhong; Zhou, Hua; Wei, YeLin; Ou, Xingyi; Huang, Jinyu; Wang, Deqiang; Li, Xiaobin; Wan, Qun; Shan, Baoju; Zhang, Zhenlin"

作者地址："[Wei, Jie; Zhang, Qinghuan; Lu, Jinping; Ou, Xingyi; Zhang, Zhenlin] Jinan Univ, Zhuhai Clin Med Coll, Zhuhai Peoples Hosp, Dept Clin Lab, Zhuhai, Peoples R China; [Shen, Shimei; Mao, Shenglan; Zou, Chunhong; Huang, Jinyu; Wang, Deqiang] Chongqing Med Univ, Key Lab Mol Biol Infect Dis, Inst Viral Hepatitis, Dept Infect Dis,Minist Educ,Affiliated Hosp 2, Chongqing, Peoples R China; [Zhou, Hua] Chongqing Med Univ, Affiliated Hosp 2, Dept Clin Lab, Chongqing, Peoples R China; [Wei, YeLin] First Peoples Hosp Xiaoshan Hangzhou, Hangzhou 311200, Peoples R China; [Li, Xiaobin] Jinan Univ, Zhuhai Hosp, Zhuhai Precis Med Ctr, Zhuhai Peoples Hosp, Zhuhai, Peoples R China; [Wan, Qun] Sun Yat Sen Univ, Affiliated Hosp 5, Dept Clin Lab, Zhuhai, Peoples R China; [Shan, Baoju] Chongqing Med Univ, Pediat Res Inst, Chongqing, Peoples R China; [Shan, Baoju] Chongqing Med Univ, Minist Educ, Key Lab Child Dev & Disorders, Chongqing, Peoples R China; [Shan, Baoju] Chongqing Med Univ, Natl Clin Res Ctr Child Hlth & Disorders, Chongqing, Peoples R China; [Shan, Baoju] Chongqing Med Univ, China Int Sci & Technol Cooperat Base Child Dev &, Childrens Hosp, Chongqing, Peoples R China; [Shan, Baoju] Chongqing Med Univ, Chongqing Key Lab Pediat, Childrens Hosp, Chongqing, Peoples R China"

通信作者："Zhang, ZL (通讯作者)，Jinan Univ, Zhuhai Clin Med Coll, Zhuhai Peoples Hosp, Dept Clin Lab, Zhuhai, Peoples R China.; Wan, Q (通讯作者)，Sun Yat Sen Univ, Affiliated Hosp 5, Dept Clin Lab, Zhuhai, Peoples R China.; Shan, BJ (通讯作者)，Chongqing Med Univ, Pediat Res Inst, Chongqing, Peoples R China.; Shan, BJ (通讯作者)，Chongqing Med Univ, Minist Educ, Key Lab Child Dev & Disorders, Chongqing, Peoples R China.; Shan, BJ (通讯作者)，Chongqing Med Univ, Natl Clin Res Ctr Child Hlth & Disorders, Chongqing, Peoples R China.; Shan, BJ (通讯作者)，Chongqing Med Univ, China Int Sci & Technol Cooperat Base Child Dev &, Childrens Hosp, Chongqing, Peoples R China.; Shan, BJ (通讯作者)，Chongqing Med Univ, Chongqing Key Lab Pediat, Childrens Hosp, Chongqing, Peoples R China."

来源：EUROPEAN JOURNAL OF CLINICAL MICROBIOLOGY & INFECTIOUS DISEASES

ESI学科分类：MICROBIOLOGY

WOS号：WOS:001180386700001

JCR分区：Q2

影响因子：3.7

年份：2024

卷号：　

期号：　

开始页：　

结束页：　

文献类型：Article; Early Access

关键词："Ceftazidime-avibactam; Salmonella enterica serovar 1,4,[5]; 12: i: -; Bla(CTX-M-261); Bla(NDM-5); IncI1-I(alpha)"

摘要："Purpose The detection rate of Salmonella enterica serovar 1,4,[5], 12: i: - (S. 1,4,[5], 12: i: -) has increased as the most common serotype globally. A S. 1,4,[5], 12: i: - strain named ST3606 (sequence type 34), isolated from a fecal specimen of a child with acute diarrhea hospitalized in a tertiary hospital in China, was firstly reported to be resistant to carbapenem and ceftazidime-avibactam. The aim of this study was to characterize the whole-genome sequence of S. 1,4,[5], 12: i: - isolate, ST3606, and explore its antibiotic resistance genes and their genetic environments. Methods The genomic DNA of S. 1,4,[5], 12: i: - ST3606 was extracted and performed with single-molecule real-time sequencing. Resistance genes, plasmid replicon type, mobile elements, and multilocus sequence types (STs) of ST3606 were identified by ResFinder 3.2, PlasmidFinder, OriTfinder database, ISfinder database, and MLST 2.0, respectively. The conjugation experiment was utilized to evaluate the conjugation frequency of pST3606-2. Protein expression and enzyme kinetics experiments of CTX-M were performed to analyze hydrolytic activity of a novel CTX-M-261 enzyme toward several antibiotics. Results Single-molecule real-time sequencing revealed the coexistence of a 109-kb IncI1-I alpha plasmid pST3606-1 and a 70.5-kb IncFII plasmid pST3606-2. The isolate carried resistance genes, including bla(NDM-5), sul1, qacE, aadA2, and dfrA12 in pST3606-1, bla(TEM-1B), aac(3)-lld, and bla(CTX-M-261), a novel bla(CTX-M-1) family member, in pST3606-2, and aac(6')-Iaa in chromosome. The bla(CTX-M-261) was derived from bla(CTX-M-55) by a single-nucleotide mutation 751G>A leading to amino acid substitution of Val for Met at position 251 (Val251Met), which conferred CTX-M increasing resistance to ceftazidime verified by antibiotics susceptibility testing of transconjugants carrying pST3606-2 and steady-state kinetic parameters of CTX-M-261. pST3606-1 is an IncI1-alpha incompatibility type that shares homology with plasmids of pC-F-164_A-OXA140, pE-T654-NDM-5, p_dm760b_NDM-5, and p_dmcr749c_NDM-5. The conjugation experiment demonstrated that pST3606-2 was successfully transferred to the Escherichia coli recipient C600 with four modules of OriTfinder. Conclusion Plasmid-mediated horizontal transfer plays an important role in bla(NDM-5) and bla(CTX-M-261) dissemination, which increases the threat to public health due to the resistance to most beta-lactam antibiotics. This is the first report of bla(CTX-M-261) and bla(NDM-5) in S. 1,4,[5], 12: i: -. The work provides insights into the enzymatic function and demonstrates the ongoing evolution of CTX-M enzymes and confirms urgency to control resistance of S. 1,4,[5], 12: i: -"

基金机构：GuangDong Basic and Applied Basic Research Foundation

基金资助正文：The authors are very grateful to Prof. Xiaobin Li for their excellent technical assistance as well as constructive comments and recommendations. The authors would like to thank Suzhou Genewiz Biotechnology Co. Ltd. for the sequencing of the bacteria.