Genome Analysis of Colistin-resistant Isolates from Human Sources in Guizhou of Southwestern China, 2019-2023

Overview

Journal Front Microbiol

Specialty Microbiology

Date 2025 Feb 13

PMID 39944652

Authors

Jingtong Wu

Yongxian Wen

Lv You

Xiaoyu Wei

Junhua Wang

Ge Zhu

ShiJun Li

Affiliations

Soon will be listed here.

Abstract

Background: Colistin is commonly used as a last-resort antibiotic for multidrug resistance (MDR) bacterial infections. The emergence of colistin-resistant (CL-R) has become a significant public health concern. However, the prevalence of CL-R in Guizhou province remains unknown. Therefore, it is necessary to monitor CL-R in Guizhou and systematically elucidate their characteristics-related resistance, virulence, and molecular epidemiology to develop effective public health strategies against resistant pathogens.

Methods: The CL-R isolates were identified from 933 isolates by antimicrobial resistance testing. To further evaluate the molecular epidemiology, the CL-R isolates underwent whole-genome sequencing (WGS) analysis followed by bioinformatic analysis.

Results: A total of 43 CL-R isolates (4.6%) were identified from 933 isolates, of which 39 isolates being MDR (resistance to three or more classes of antimicrobials). WGS analysis revealed 34 antibiotic resistance genes (ARGs), and point mutations in the gene (D87Y and D87G) were identified in all 43 CL-R isolates. Only one isolate carried the mcr-1.1 gene, a known colistin resistance. All CL-R isolates were found to carry multidrug efflux pumps. Furthermore, the most common resistance gene was (40 out of 43), followed by (39 out of 43). The majority of CL-R isolates contained the virulence factor and a notable diversity in other virulence factors with varied functions. Core genome multilocus sequence typing (cgMLST) revealed that 43 CL-R isolates were divided into 19 cgSTs, with cgST179151 (10 out of 43) being the most prevalent. Additionally, the CL-R isolates exhibited genetic similarities with human isolates from Poland, Canada, and Zhejiang province. Among the 42 CL-R isolates lacking markers for CL-R, 12 single-nucleotide variations (SNVs) were observed in 24 isolates using genome-wide association study (GWAS) analysis, which was possibly associated with colistin resistance.

Conclusion: This study revealed that the majority of CL-R isolates in Guizhou province exhibited MDR, with complex resistance mechanisms, representing a significant public health challenge. The genetic similarities between isolates from Guizhou and other regions suggested the possibility of international transmission or shared reservoirs of resistance. These results highlighted the urgent need for enhanced surveillance and effective public health strategies to address the risks posed by these pathogens in Guizhou.

References

Misra R, Thakare R, Amrin N, Prasad K, Chopra S, Dhole T . Antimicrobial susceptibility pattern and sequence analysis of DNA gyrase and DNA topoisomerase IV in Salmonella enterica serovars Typhi and Paratyphi A isolates with decreased susceptibility to ciprofloxacin. Trans R Soc Trop Med Hyg. 2016; 110(8):472-9. DOI: 10.1093/trstmh/trw051. View

Cheng Q, Cheung Y, Chan E, Wong K, Chen S . Unveiling the evolution routes of TEM-type extended-spectrum β-lactamases. Int J Antimicrob Agents. 2021; 59(1):106498. DOI: 10.1016/j.ijantimicag.2021.106498. View

Elbediwi M, Li Y, Paudyal N, Pan H, Li X, Xie S . Global Burden of Colistin-Resistant Bacteria: Mobilized Colistin Resistance Genes Study (1980-2018). Microorganisms. 2019; 7(10). PMC: 6843232. DOI: 10.3390/microorganisms7100461. View

Algammal A, Hetta H, Mabrok M, Behzadi P . Editorial: Emerging multidrug-resistant bacterial pathogens "superbugs": A rising public health threat. Front Microbiol. 2023; 14:1135614. PMC: 9930894. DOI: 10.3389/fmicb.2023.1135614. View

Nirwan P, Chatterjee N, Panwar R, Dudeja M, Jaggi N . Mutations in two component system (PhoPQ and PmrAB) in colistin resistant Klebsiella pneumoniae from North Indian tertiary care hospital. J Antibiot (Tokyo). 2021; 74(7):450-457. DOI: 10.1038/s41429-021-00417-2. View

Agerso Y, Torpdahl M, Zachariasen C, Seyfarth A, Hammerum A, Nielsen E . Tentative colistin epidemiological cut-off value for Salmonella spp. Foodborne Pathog Dis. 2012; 9(4):367-9. DOI: 10.1089/fpd.2011.1015. View

Aghapour Z, Gholizadeh P, Ganbarov K, Zahedi Bialvaei A, Mahmood S, Tanomand A . Molecular mechanisms related to colistin resistance in Enterobacteriaceae. Infect Drug Resist. 2019; 12:965-975. PMC: 6519339. DOI: 10.2147/IDR.S199844. View

Wei X, Long L, You L, Wang M, Wang D, Liu C . Serotype distribution, trend of multidrug resistance and prevalence of β-lactamase resistance genes in human Salmonella isolates from clinical specimens in Guizhou, China. PLoS One. 2023; 18(4):e0282254. PMC: 10118202. DOI: 10.1371/journal.pone.0282254. View

Ricci V, Zhang D, Teale C, Piddock L . The O-Antigen Epitope Governs Susceptibility to Colistin in Salmonella enterica. mBio. 2020; 11(1). PMC: 6989106. DOI: 10.1128/mBio.02831-19. View

10.

Liu Y, Wang Y, Walsh T, Yi L, Zhang R, Spencer J . Emergence of plasmid-mediated colistin resistance mechanism MCR-1 in animals and human beings in China: a microbiological and molecular biological study. Lancet Infect Dis. 2015; 16(2):161-8. DOI: 10.1016/S1473-3099(15)00424-7. View

11.

Zhao L, Liu G, Tang W, Song X, Zhao X, Wang C . Antimicrobial resistance and genomic characteristics of from broilers in Shandong Province. Front Vet Sci. 2023; 10:1292401. PMC: 10701519. DOI: 10.3389/fvets.2023.1292401. View

12.

Kempf I, Jouy E, Chauvin C . Colistin use and colistin resistance in bacteria from animals. Int J Antimicrob Agents. 2016; 48(6):598-606. DOI: 10.1016/j.ijantimicag.2016.09.016. View

13.

Jajere S . A review of with particular focus on the pathogenicity and virulence factors, host specificity and antimicrobial resistance including multidrug resistance. Vet World. 2019; 12(4):504-521. PMC: 6515828. DOI: 10.14202/vetworld.2019.504-521. View

14.

Jain C, Rodriguez-R L, Phillippy A, Konstantinidis K, Aluru S . High throughput ANI analysis of 90K prokaryotic genomes reveals clear species boundaries. Nat Commun. 2018; 9(1):5114. PMC: 6269478. DOI: 10.1038/s41467-018-07641-9. View

15.

Hansen H, Heisig P . Topoisomerase IV mutations in quinolone-resistant salmonellae selected in vitro. Microb Drug Resist. 2003; 9(1):25-32. DOI: 10.1089/107662903764736319. View

16.

Guo L, Xiao T, Wu L, Li Y, Duan X, Liu W . Comprehensive profiling of serotypes, antimicrobial resistance and virulence of isolates from food animals in China, 2015-2021. Front Microbiol. 2023; 14:1133241. PMC: 10110913. DOI: 10.3389/fmicb.2023.1133241. View

17.

Galvao L, Rosalen P, Rivera-Ramos I, Franco G, Kajfasz J, Abranches J . Inactivation of the spxA1 or spxA2 gene of Streptococcus mutans decreases virulence in the rat caries model. Mol Oral Microbiol. 2016; 32(2):142-153. PMC: 5045749. DOI: 10.1111/omi.12160. View

18.

Kuang D, Zhang J, Xu X, Shi W, Yang X, Su X . Increase in Ceftriaxone Resistance and Widespread Extended-Spectrum β-Lactamases Genes Among Salmonella enterica from Human and Nonhuman Sources. Foodborne Pathog Dis. 2018; 15(12):770-775. DOI: 10.1089/fpd.2018.2468. View

19.

Ahmed M, Zhong L, Shen C, Yang Y, Doi Y, Tian G . Colistin and its role in the Era of antibiotic resistance: an extended review (2000-2019). Emerg Microbes Infect. 2020; 9(1):868-885. PMC: 7241451. DOI: 10.1080/22221751.2020.1754133. View

20.

Gurvic D, Zachariae U . Multidrug efflux in Gram-negative bacteria: structural modifications in active compounds leading to efflux pump avoidance. NPJ Antimicrob Resist. 2025; 2(1):6. PMC: 11721645. DOI: 10.1038/s44259-024-00023-w. View