Unveiling the Global Threat: Genomic Insights into Carbapenem-Resistant Salmonella enterica subsp . enterica in Human

Abstract

The misuse of broad-spectrum antibiotics has facilitated the emergence of carbapenem-resistant Salmonella enterica subsp. enterica (CRSE). This study aims to investigate the genomic characteristics and epidemiological patterns of two strains isolated from pediatric patients, along with 21 CRSE strains collected from humans worldwide. The antimicrobial susceptibility tests were detected by the agar microdilution method. Whole-genome sequence of the two CRSE strains was sequenced using the Illumina platform. Acquisition and analysis of WGS data were performed by the NCBI Pathogen Detection Portal, BacWGSTdb 2.0, Salmonella In Silico Typing Resource, and the Center for Genomic Epidemiology. Two S. Typhimurium isolates from children carried the carbapenemase gene bla_NDM-5 and belonged to ST34. The CRSE isolates predominantly contained the carbapenem resistance gene bla_OXA-48 in the United Kingdom and bla_NDM in China. The virulence gene profiles of these isolates were consistent across different regions. Carbapenem-resistant S. Typhimurium and S. Kentucky were predominantly found in China and the United Kingdom, respectively. ST198 strains were prevalent in the United Kingdom, whereas all ST34 strains were identified in China. This investigation underscores the global dissemination of carbapenem-resistant Salmonella in humans, revealing variations in drug resistance, serotypes, and sequence types across different regions. Therefore, the global detection of carbapenem resistance has important guiding significance for controlling its transmission, preventing infection, and clinical treatment.

Keywords

carbapenem resistance global location prevalence

Get full access to this article

View all access options for this article.

References

1.GBD 2017 Non-Typhoidal Salmonella Invasive Disease Collaborators. The global burden of non-typhoidal salmonella invasive disease: A systematic analysis for the global burden of disease study 2017. Lancet Infect Dis 2019;19(12):1312–1324; doi: 10.1016/S1473-3099(19)30418-9

2. Fabrega

, Vila

. Salmonella enterica serovar typhimurium skills to succeed in the host: Virulence and regulation. Clin Microbiol Rev 2013;26(2):308–341; doi: 10.1128/CMR.00066-12

3. Nazari Moghadam

, Rahimi

, Shakerian

, et al. Prevalence of salmonella typhimurium and salmonella Enteritidis isolated from poultry meat: Virulence and antimicrobial-resistant genes. BMC Microbiol 2023;23(1):168; doi: 10.1186/s12866-023-02908-8

4. Williams

, Markey

, Harlock

, et al. Individual and household-level risk factors for sporadic salmonellosis in children. J Infect 2016;72(1):36–44; doi: 10.1016/j.jinf.2015.09.014

Majowicz

, Musto

, Scallan

, International Collaboration on Enteric Disease ‘Burden of Illness’ Studies

et al.;. The global burden of nontyphoidal salmonella gastroenteritis. Clin Infect Dis 2010;50(6):882–889; doi: 10.1086/650733

Tacconelli

, Carrara

, Savoldi

, WHO Pathogens Priority List Working Group

et al.. Discovery, research, and development of new antibiotics: The WHO priority list of antibiotic-resistant bacteria and tuberculosis. Lancet Infect Dis 2018;18(3):318–327; doi: 10.1016/S1473-3099(17)30753-3

7. Guibourdenche

, Roggentin

, Mikoleit

, et al. (Supplement 2003–2007 (No. 47) to the White-Kauffmann-Le minor scheme. Res Microbiol 2010;161(1):26–29; doi: 10.1016/j.resmic.2009.10.002

8. Feng

, Zou

, Chen

, et al. BacWGSTdb 2.0: A one-stop repository for bacterial whole-genome sequence typing and source tracking. Nucleic Acids Res 2021;49(D1):D644–D650; doi: 10.1093/nar/gkaa821

9. Yoshida

, Kruczkiewicz

, Laing

, et al. The salmonella in silico typing resource (SISTR): An open web-accessible tool for rapidly typing and subtyping draft salmonella genome assemblies. PLoS One 2016;11(1):e0147101; doi: 10.1371/journal.pone.0147101

10.

10. Li

, Lai

, Wang

, et al. Prevalence and characterization of salmonella species isolated from pigs, ducks and chickens in Sichuan province, China. Int J Food Microbiol 2013;163(1):14–18; doi: 10.1016/j.ijfoodmicro.2013.01.020

11.

11. Oscar

. Initial contamination of chicken parts with salmonella at retail and cross-contamination of cooked chicken with salmonella from raw chicken during meal preparation. J Food Prot 2013;76(1):33–39; doi: 10.4315/0362-028X.JFP-12-224

12.

12. Aulicino

, Rue-Albrecht

, Preciado-Llanes

, et al. Invasive salmonella exploits divergent immune evasion strategies in infected and bystander dendritic cell subsets. Nat Commun 2018;9(1):4883; doi: 10.1038/s41467-018-07329-0

13.

13. Wong

, Yan

, Chan

, et al. Expansion of salmonella enterica serovar typhimurium ST34 clone carrying multiple resistance determinants in China. Antimicrob Agents Chemother 2013;57(9):4599–4601; doi: 10.1128/AAC.01174-13

14.

14. El-Gamal

, Brahim

, Hisham

, et al. Recent updates of carbapenem antibiotics. Eur J Med Chem 2017;131:185–195; doi: 10.1016/j.ejmech.2017.03.022

15.

15. Zhang

, Fang

, Zhang

, et al. Carbapenemase- and colistin resistant escherichia coli strains from children in China: High genetic diversity and first report of bla (NDM-5), bla (CTX-M-65), bla (OXA-10), bla (TEM-1), and mcr-1.1 genes co-occurrence in E. coli ST156. IDR 2022;15:5315–5320; doi: 10.2147/IDR.S378574

16.

16. Hurst

, Berend

. Mobile-bearing unicondylar knee arthroplasty: The Oxford experience. Clin Sports Med 2014;33(1):105–121; doi: 10.1016/j.csm.2013.06.004

17.

17. Sarkar

, Pazhani

, Chowdhury

, et al. Attributes of carbapenemase encoding conjugative plasmid pNDM-SAL from an extensively drug-resistant salmonella enterica serovar senftenberg. Front Microbiol 2015;6:969; doi: 10.3389/fmicb.2015.00969

18.

18. Day

, Meunier

, Doumith

, et al. Carbapenemase-producing salmonella enterica isolates in the UK. J Antimicrob Chemother 2015;70(7):2165–2167; doi: 10.1093/jac/dkv075

19.

19. Jure

, Duprilot

, Musa

, et al. Emergence of KPC-2-producing salmonella enterica serotype schwarzengrund in Argentina. Antimicrob Agents Chemother 2014;58(10):6335–6336; doi: 10.1128/AAC.03322-14

20.

20. Fernandez

, Guerra

, Rodicio

. Resistance to carbapenems in non-typhoidal salmonella enterica serovars from humans, animals and food. Vet Sci 2018;5(2):40; doi: 10.3390/vetsci5020040

21.

21. Hsu

, Wang

, Chen

, et al. Carbapenem resistance in extensively drug-resistant salmonella enterica serovar Agona and AmpC beta-lactamase-producing S. Infantis. Microbiol Spectr 2023;11(6):e0292223; doi: 10.1128/spectrum.02922-23

22.

22. Armand-Lefevre

, Leflon-Guibout

, Bredin

, et al. Imipenem resistance in salmonella enterica serovar wien related to porin loss and CMY-4 beta-lactamase production. Antimicrob Agents Chemother 2003;47(3):1165–1168; doi: 10.1128/AAC.47.3.1165-1168.2003

23.

23. Zhou

, Shi

, Zhang

, et al. Salmonella enterica subsp. Diarizonae harboring ST233, ST1263, and ST1845 in children. Front Cell Infect Microbiol 2021;11:727811; doi: 10.3389/fcimb.2021.727811

24.

24. Fischbach

, Lin

, Liu

, et al. How pathogenic bacteria evade mammalian sabotage in the battle for iron. Nat Chem Biol 2006;2(3):132–138; doi: 10.1038/nchembio771

25.

25. Spiga

, Fansler

, Perera

, et al. Iron acquisition by a commensal bacterium modifies host nutritional immunity during salmonella infection. Cell Host Microbe 2023;31(10):1639–1654e10; doi: 10.1016/j.chom.2023.08.018

26.

26. Saha

, Xiao

, Yeoh

, et al. The bacterial siderophore enterobactin confers survival advantage to salmonella in macrophages. Gut Microbes 2019;10(3):412–423; doi: 10.1080/19490976.2018.1546519

27.

27. Alix

, Blanc-Potard

. Peptide-assisted degradation of the salmonella MgtC virulence factor. Embo J 2008;27(3):546–557; doi: 10.1038/sj.emboj.7601983

28.

28. Alix

, Blanc-Potard

. MgtC: A key player in intramacrophage survival. Trends Microbiol 2007;15(6):252–256; doi: 10.1016/j.tim.2007.03.007

29.

29. Sheng

, Wang

, Chen

, et al. Mig-14 may contribute to salmonella enterica serovar Typhi resistance to polymyxin B by decreasing the permeability of the outer-membrane and promoting the formation of biofilm. Int J Med Microbiol 2019;309(2):143–150; doi: 10.1016/j.ijmm.2019.01.001

30.

30. Hawkey

, Le Hello

, Doublet

, et al. Global phylogenomics of multidrug-resistant salmonella enterica serotype Kentucky ST198. Microb Genom 2019;5(7):e000269; doi: 10.1099/mgen.0.000269

31.

31. Wu

, Jiang

, Bao

, et al. Global population structure and genomic surveillance framework of carbapenem-resistant salmonella enterica. Drug Resist Updat 2023;68:100953; doi: 10.1016/j.drup.2023.100953

32.

32. Biswas

, Li

, Elbediwi

, et al. Emergence and dissemination of mcr-carrying clinically relevant salmonella typhimurium monophasic clone ST34. Microorganisms 2019;7(9):298; doi: 10.3390/microorganisms7090298

33.

33. Wu

, Du

, Zhou

, et al. Genomic epidemiology and public health implications of zoonotic monophasic salmonella typhimurium ST34. Front Cell Infect Microbiol 2025;15:1490183; doi: 10.3389/fcimb.2025.1490183

34.

34. Huang

, Wang

, Ding

, et al. New Delhi metallo-beta-lactamase-1 in carbapenem-resistant Salmonella strain, China. Emerg Infect Dis 2013;19(12):2049–2051; doi: 10.3201/eid1912.130051

35.

35. Zeng

, Huang

, Zhang

, et al. Molecular characterization of IncFII plasmid carrying bla(NDM-5) in a salmonella enterica serovar typhimurium ST34 clinical isolate in China. mSphere 2023;8(6):e0048023; doi: 10.1128/msphere.00480-23

36.

36. Deng

, Lv

, Tu

, et al. Clonal spread of blaNDM-1-carrying salmonella enterica serovar typhimurium clone ST34 and wide spread of IncHI2/ST3-blaNDM-5 plasmid in China. J Antimicrob Chemother 2024;79(8):1900–1909; doi: 10.1093/jac/dkae178

37.

37. Ke

, Zhu

, Lu

, et al. Emerging bla(NDM)-positive Salmonella enterica in Chinese pediatric infections. Microbiol Spectr 2024;12(12):e0148524; doi: 10.1128/spectrum.01485-24

Supplementary Material

Please find the following supplemental material available below.

For Open Access articles published under a Creative Commons License, all supplemental material carries the same license as the article it is associated with.

For non-Open Access articles published, all supplemental material carries a non-exclusive license, and permission requests for re-use of supplemental material or any part of supplemental material shall be sent directly to the copyright owner as specified in the copyright notice associated with the article.

0.00 MB

1.30 MB

0.69 MB