Dataset Information

Molecular Genetic Characteristics of Plasmid-Borne mcr-9 in Salmonella enterica Serotype Typhimurium and Thompson in Zhejiang, China.

ABSTRACT: Salmonella enterica is a zoonotic food-borne pathogen threatening public health around the world. As is the case with many other pathogens, the spread of mobilized colistin resistance (mcr) alleles is of grave concern. In this study, totally 689 clinical Salmonella isolates were collected from a local hospital in Hangzhou, Zhejiang Province, China between 2009 and 2018. Resistance genes were screen by PCR. Two mcr-9-positive Salmonella strains S15 and S639 were identified which belong to serotype Typhimurium and Thompson, respectively. We observed that both mcr-9 genes were located on conjugative IncHI2 plasmids which encoded numerous resistance genes, likely facilitating the dissemination of mcr-9 by co-resistance mechanisms. The mcr-9 cassettes encoded on the two plasmids were not identical: downstream of the mcr-9 genes, we found IS1 on one plasmid (pS15), while the other had a WbuC-IS26 (pS639). Despite the presence of mcr-9 cassettes, the strains were not rendered colistin resistant. Yet, it is of epidemiological importance to implement surveillance to be able to observe and possibly control the spread of mcr-9 due to its potential to mediate resistance to the last-resort antibiotic colistin.

SUBMITTER: Fan J

PROVIDER: S-EPMC8969412 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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Publications

Molecular Genetic Characteristics of Plasmid-Borne mcr-9 in Salmonella enterica Serotype Typhimurium and Thompson in Zhejiang, China.

Fan Jianzhong J Cai Heng H Fang Youhong Y He Jintao J Zhang Linghong L Xu Qingye Q Yang Yunxing Y Leptihn Sebastian S Yu Yunsong Y Zhao Dongdong D Hua Xiaoting X

Frontiers in microbiology 20220317

Salmonella enterica is a zoonotic food-borne pathogen threatening public health around the world. As is the case with many other pathogens, the spread of mobilized colistin resistance (mcr) alleles is of grave concern. In this study, totally 689 clinical Salmonella isolates were collected from a local hospital in Hangzhou, Zhejiang Province, China between 2009 and 2018. Resistance genes were screen by PCR. Two mcr-9-positive Salmonella strains S15 and S639 were ...[more]

PMID: 35369459

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Project description:Mobilized colistin resistance (mcr) genes are plasmid-borne genes that confer resistance to colistin, an antibiotic used to treat severe bacterial infections. To date, eight known mcr homologues have been described (mcr-1 to -8). Here, we describe mcr-9, a novel mcr homologue detected during routine in silico screening of sequenced Salmonella genomes for antimicrobial resistance genes. The amino acid sequence of mcr-9, detected in a multidrug-resistant (MDR) Salmonella enterica serotype Typhimurium (S Typhimurium) strain isolated from a human patient in Washington State in 2010, most closely resembled mcr-3, aligning with 64.5% amino acid identity and 99.5% coverage using Translated Nucleotide BLAST (tblastn). The S. Typhimurium strain was tested for phenotypic resistance to colistin and was found to be sensitive at the 2-mg/liter European Committee on Antimicrobial Susceptibility Testing breakpoint under the tested conditions. mcr-9 was cloned in colistin-susceptible Escherichia coli NEB5α under an IPTG (isopropyl-β-d-thiogalactopyranoside)-induced promoter to determine whether it was capable of conferring resistance to colistin when expressed in a heterologous host. Expression of mcr-9 conferred resistance to colistin in E. coli NEB5α at 1, 2, and 2.5 mg/liter colistin, albeit at a lower level than mcr-3 Pairwise comparisons of the predicted protein structures associated with all nine mcr homologues (Mcr-1 to -9) revealed that Mcr-9, Mcr-3, Mcr-4, and Mcr-7 share a high degree of similarity at the structural level. Our results indicate that mcr-9 is capable of conferring phenotypic resistance to colistin in Enterobacteriaceae and should be immediately considered when monitoring plasmid-mediated colistin resistance.IMPORTANCE Colistin is a last-resort antibiotic that is used to treat severe infections caused by MDR and extensively drug-resistant (XDR) bacteria. The World Health Organization (WHO) has designated colistin as a "highest priority critically important antimicrobial for human medicine" (WHO, Critically Important Antimicrobials for Human Medicine, 5th revision, 2017, https://www.who.int/foodsafety/publications/antimicrobials-fifth/en/), as it is often one of the only therapies available for treating serious bacterial infections in critically ill patients. Plasmid-borne mcr genes that confer resistance to colistin pose a threat to public health at an international scale, as they can be transmitted via horizontal gene transfer and have the potential to spread globally. Therefore, the establishment of a complete reference of mcr genes that can be used to screen for plasmid-mediated colistin resistance is essential for developing effective control strategies.

Project description:Regulation of flagellum biosynthesis is a hierarchical process that is tightly controlled to allow for efficient tuning of flagellar expression. Flagellum-mediated motility directs Salmonella enterica serovar Typhimurium toward the epithelial surface to enhance gut colonization, but flagella are potent activators of innate immune signaling, so fine-tuning flagellar expression is necessary for immune avoidance. In this work, we evaluate the role of the LysR transcriptional regulator YeiE in regulating flagellum-mediated motility. We show that yeiE is necessary and sufficient for swimming motility. A ΔyeiE mutant is defective for gut colonization in both the calf ligated ileal loop model and the murine colitis model due to its lack of motility. Expression of flagellar class 2 and 3 but not class 1 genes is reduced in the ΔyeiE mutant. We linked the motility dysregulation of the ΔyeiE mutant to repression of the anti-FlhD4C2 factor STM1697. Together, our results indicate that YeiE promotes virulence by enhancing cell motility, thereby providing a new regulatory control point for flagellar expression in Salmonella Typhimurium. IMPORTANCE The ability to finely tune virulence factor gene expression is required for bacterial pathogens to successfully colonize a host. Flagellum-mediated motility is critical for many gut pathogens to establish productive infections. However, flagella activate the immune system, leading to bacterial clearance; therefore, tight control of flagellar gene expression enhances bacterial fitness in the host. Here, we demonstrate that the transcriptional regulator YeiE acts as a control point for flagellar gene expression and is required for Salmonella Typhimurium to establish a productive infection in mammals. The expression of an inhibitor of flagellar biogenesis is repressed in the absence of yeiE. Our work adds a new layer to the tightly controlled cascade regulating control of flagellar gene expression to facilitate the fitness of an enteric pathogen.

Dataset Information

Molecular Genetic Characteristics of Plasmid-Borne mcr-9 in Salmonella enterica Serotype Typhimurium and Thompson in Zhejiang, China.

Publications

Molecular Genetic Characteristics of Plasmid-Borne <i>mcr-9</i> in <i>Salmonella enterica</i> Serotype Typhimurium and Thompson in Zhejiang, China.

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