Please wait a minute...
Journal of Integrative Agriculture
Advanced Online Publication | Current Issue | Archive | Adv Search
Prophage mediate the emergence of NDM-13-positive monophasic Salmonella Indiana by imprecise excision

Zhenyu Wang1,2*, Yue Jiang1,2*, Pengyun Shao1,2, Xinan Jiao1,2, Jing Wang3#, Qiuchun Li1,2#

1 Jiangsu Key Laboratory of Zoonosis/Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou University, Yangzhou 225009, China

2 Key Laboratory of Prevention and Control of Biological Hazard Factors (Animal Origin) for Agrifood Safety and Quality, Ministry of Agriculture of China, Yangzhou University, Yangzhou 225009, China

3 Institute of Medical Sciences, School of Public Health, Xinjiang Medical University, Urumqi 830017, China

 Highlights 

A monophasic Salmonella Indiana variant was isolated from chicken meat in China.

The variant arose via prophage-mediated imprecise excision replacing the fljAB operon and adjacent genes with ΦSM.

An IncHI2 plasmid carrying two MRRs including the carbapenem resistant gene blaNDM-13 was reported in Salmonella for the first time.

Download:  PDF in ScienceDirect  
Export:  BibTeX | EndNote (RIS)      
摘要  

目的:近年来,因相鞭毛基因被耐药基因或噬菌体序列替代而产生的沙门菌单相变异株不断出现并流行。碳青霉烯耐药株的出现对公共卫生安全构成严重威胁。本研究旨在解析一株NDM-13阳性印第安那沙门菌单相变异体的基因组特征、耐药谱、遗传演化特点及产生机制。

方法:采用微量肉汤稀释法或琼脂稀释法检测菌株对14种抗菌药物的敏感性;同时利用传统玻片凝集法进行血清学分型,并结合Salmonella In Silico Typing ResourceSISTR)对基因组进行血清型预测。随后,应用多位点序列分型(MLST)和核心基因组MLSTcgMLST)解析其系统发育特征;通过比较基因组学揭示前噬菌体整合与Ⅱ相鞭毛基因缺失的机制;并对所携带质粒的耐药基因组成和结构进行系统解析,结合接合实验评估其水平传播潜力。

结果:血清学鉴定结合MLSTcgMLST分析结果证实,该菌株为印第安那沙门菌的单相变异体。比较基因组学进一步揭示,其Ⅱ相鞭毛基因簇fljAB及邻近七个基因被来源于S. Mbanada的一个8.9 kb截短前噬菌体(ΔΦSM)取代。ΦSM介导的不精确切除导致了fljAB基因簇及周边序列丢失,从而驱动了单相变异体的形成。耐药性分析表明,该菌株携带一条IncHI2质粒,包含两个多重耐药区(MRRs)。除常见的blaTEM-1BblaCTX-M-65strAstrBsul2外,质粒中还存在一段长达51.3 kb的额外MRR,插入于dam基因,携带aph(3)-IIaaadA22blaNDM-13mph(A)erm(B),赋予菌株对卡那霉素、链霉素、碳青霉烯类、阿奇霉素和林可霉素的耐药性。但由于IS26介导的转座导致接合区缺失,该质粒在实验条件下未能实现接合转移。

结论:本研究阐明了前噬菌体不精确切除介导NDM-13阳性印地安纳单相变异体产生的分子机制,并揭示了其携带的复杂耐药质粒结构。结果表明,前噬菌体与可移动遗传元件的协同作用可以推动耐药性沙门菌单相变异体产生与演化。

创新性:本研究首次证实前噬菌体不精确切除在NDM-13阳性印第安纳单相变异体形成中的关键作用,并揭示了其独特的耐药质粒进化特征。这不仅拓展了对单相型沙门菌分子进化机制的认识,也为基于全基因组测序的耐药性监测与食源性病原菌预警提供了新的理论依据和实践思路。



Online: 01 November 2025  
Fund: 

This study was supported by the National Key Research and Development Program of China (2022YFC2604200, 2024YFE0198800, and 2023YFD1800503), the Open Co-operation Project of Center for Global Health (JX103SYL2024060102), the fifth phase of “333 Project” Scientific Research project in Jiangsu Province, China (BRA2020002), the Priority Academic Program Development of Jiangsu Higher Education Institutions, China (PAPD), and the 111 Project (D18007).

About author:  #Correspondence Jing Wang, Tel: +86-514-87971136, Fax: +86-514-87991747, E-mail: wj1231@xjmu.edu.cn, Qiuchun Li, E-mail: qcli@yzu.edu.cn; * These authors contributed equally to this article.

Cite this article: 

Zhenyu Wang, Yue Jiang, Pengyun Shao, Xinan Jiao, Jing Wang, Qiuchun Li. 2025. Prophage mediate the emergence of NDM-13-positive monophasic Salmonella Indiana by imprecise excision. Journal of Integrative Agriculture, Doi:10.1016/j.jia.2025.10.021

Bai L, Lan R, Zhang X, Cui S, Xu J, Guo Y, Li F, Zhang D. 2015. Prevalence of Salmonella isolates from chicken and pig slaughterhouses and emergence of ciprofloxacin and cefotaxime co-resistant S. enterica serovar Indiana in Henan, China. PLoS One, 10, e0144532.

Banerji S, Simon S, Tille A, Fruth A, Flieger A. 2020. Genome-based Salmonella serotyping as the new gold standard. Scientific Reports, 10, 4333.

Boyd E F, Brüssow H. 2002. Common themes among bacteriophage-encoded virulence factors and diversity among the bacteriophages involved. Trends in Microbiology, 10, 521–529.

Chao G, Wang C, Wu T, Zhang X, Chen J, Qi X, Cao Y, Wu Y, Jiao X. 2017. Molecular epidemiology and antibiotic resistance phenotypes and genotypes of salmonellae from food supply chains in China. Food Control, 77, 32–40.

Clinical and Laboratory Standards Institute. Performance Standards for Antimicrobial Susceptibility Testing: 32th Edition M100. Wayne: CLSI; 2022.

Du P, Liu X, Liu Y, Li R, Lu X, Cui S, Wu Y, Fanning S, Bai L. 2022. Dynamics of antimicrobial resistance and genomic epidemiology of multidrug-resistant Salmonella enterica serovar Indiana ST17 from 2006 to 2017 in China. mSystems, 7, e0025322.

European Food Safety Authority & European Centre for Disease Prevention and Control. 2020. The European Union summary report on antimicrobial resistance in zoonotic and indicator bacteria from humans, animals and food in 2017/2018. EFSA Journal, 18, e06007.

He W, Gao M, Lv L, Wang J, Cai Z, Bai Y, Gao X, Gao G, Pu W, Jiao Y, Wan M, Song Q, Chen S, Liu J H. 2023. Persistence and molecular epidemiology of blaNDM-positive Gram-negative bacteria in three broiler farms: a longitudinal study (2015-2021). Journal of Hazardous Materials, 446, 130725.

Liu G, Lü X, Tian Q, Zhang W, Yi F, Zhang Y, Yu S. 2025. Deletion of Salmonella pathogenicity islands SPI-1, 2 and 3 induces substantial morphological and metabolic alternation and protective immune potential. Journal of Integrative Agriculture24, 272–289.

Lu J, Wu H, Wu S, Wang S, Fan H, Ruan H, Qiao J, Caiyin Q, Wen M. 2025. Salmonella: infection mechanism and control strategies. Microbiological Research, 292, 128013.

Majowicz S E, Musto J, Scallan E, Angulo F J, Kirk M, O'Brien S J, Jones T F, Fazil A, Hoekstra R M, International Collaboration on Enteric Disease 'Burden of Illness' Studies. 2010. The global burden of nontyphoidal Salmonella gastroenteritis. Clinical Infectious Diseases, 50, 882889.

Mead P S, Slutsker L, Dietz V, McCaig L F, Bresee J S, Shapiro C, Griffin P M, Tauxe R V. 1999. Food-related illness and death in the United States. Emerging Infectious Diseases, 5, 607–625. 

Wang Z, Gu D, Hong Y, Hu Y, Gu J, Tang Y, Zhou X, Zhang Y, Jiao X, Li Q. 2023a. Microevolution of Salmonella 4,[5],12:i:- derived from Salmonella enterica serovar Typhimurium through complicated transpositions. Cell Reports, 42, 113227.

Wang Z, He J, Li Q, Tang Y, Wang J, Pan Z, Chen X, Jiao X. 2020. First detection of NDM-5-Positive Salmonella enterica serovar Typhimurium isolated from retail pork in China. Microbial Drug Resistance, 26, 434–437. 

Wang Z, Jiang Z, Xu H, Jiao X, Li Q. 2023b. Prevalence and molecular characterization of mcr-1-positive foodborne ST34-Salmonella isolates in China. Microbiological Research, 274, 127441.

Wang Z, Xu H, Chu C, Tang Y, Li Q, Jiao X. 2021. Genomic identification of multidrug-resistant Salmonella Virchow monophasic variant causing human septic arthritis. Pathogens, 10, 536.

Woh P Y, Yeung M P S, Goggins W B 3rd, Lo N, Wong K T, Chow V, Chau K Y, Fung K, Chen Z, Ip M. 2021. Genomic epidemiology of multidrug-resistant nontyphoidal Salmonella in young children hospitalized for gastroenteritis. Microbiology Spectrum, 9, e0024821. 

Wu W, Feng Y, Tang G, Qiao F, McNally A, Zong Z. 2019. NDM metallo-β-lactamases and their bacterial producers in health care settings. Clinical Microbiology Reviews, 32, e00115–18. 

No related articles found!
No Suggested Reading articles found!