Dataset Information

Occurrence of mcr-mediated colistin resistance in Salmonella clinical isolates in Thailand.

ABSTRACT: Nontyphoidal Salmonella, an important zoonotic pathogen and a major cause of foodborne illnesses, could be a potential reservoir of plasmids harbouring mobile colistin resistance gene (mcr). This study reported, for the first time, a high rate of mcr-carrying Salmonella clinical isolates (3.3%, 24/724) in Thailand, associated with mcr-3 gene (3.0%, 22/724) in S. 4,[5],12:i:-(15.4%, 4/26), S. Typhimurium (8.8%, 5/57), and S. Choleraesuis (5.6%, 13/231). Remarkably, the increasing trends of colistin and extended-spectrum cephalosporin resistances have displayed a high agreement over the years, with a dramatic rise in the mcr-carrying Salmonella from 1.1% (6/563) during 2005-2007 to 11.2% (18/161) during 2014-2018 when CTX-M-55 became abundant. Clonal and plasmid analysis revealed that the self-transferable IncA/C and a novel hybrid IncA/C-FIIs MDR plasmids were the major vehicles to disseminate both mcr-3 and bla_CTX-M55 genes among diverse Salmonella strains, from as early as 2007. To our knowledge the occurrence of mcr-3 and the co-existence of it with bla_CTX-M-55 in S. Choleraesuis are reported here for the first time, leading to clinical concern over the treatment of the invasive salmonellosis. This study provides evidence of the potential reservoirs and vectors in the dissemination of the mcr and highlights the co-selection by colistin and/or cephalosporins.

SUBMITTER: Luk-In S

PROVIDER: S-EPMC8266838 | biostudies-literature | 2021 Jul

REPOSITORIES: biostudies-literature

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Occurrence of mcr-mediated colistin resistance in Salmonella clinical isolates in Thailand.

Luk-In Sirirat S Chatsuwan Tanittha T Kueakulpattana Naris N Rirerm Ubolrat U Wannigama Dhammika Leshan DL Plongla Rongpong R Lawung Ratana R Pulsrikarn Chaiwat C Chantaroj Siriporn S Chaichana Pattharaporn P Saksaengsopa Nattida N Shanthachol Teerarat T Techapornroong Malee M Chayangsu Sunee S Kulwichit Wanla W

Scientific reports 20210708 1

Nontyphoidal Salmonella, an important zoonotic pathogen and a major cause of foodborne illnesses, could be a potential reservoir of plasmids harbouring mobile colistin resistance gene (mcr). This study reported, for the first time, a high rate of mcr-carrying Salmonella clinical isolates (3.3%, 24/724) in Thailand, associated with mcr-3 gene (3.0%, 22/724) in S. 4,[5],12:i:-(15.4%, 4/26), S. Typhimurium (8.8%, 5/57), and S. Choleraesuis (5.6%, 13/231). Remarkably, the increasing trends of colist ...[more]

PMID: 34238964

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Project description:Mobile colistin resistance (mcr) genes are present mainly in plasmids and can disseminate clonally or horizontally via either plasmids or insertion sequences in different genomic locations among the Enterobacteriaceae. A nationwide large-scale study on mcr prevalence and transmission in nontyphoidal Salmonella isolates is still lacking. Here, we identified 140 mcr-positive Salmonella isolates out of 7,106 isolates from 29 provinces in China from 2011 to 2020. We aligned short reads to putative plasmids from long-read hybrid assemblies and predicted the plasmid backbones of non-long-read sequencing isolates to elucidate mcr transmission patterns. The mcr-1 and mcr-3 genes are transmitted on similar high-risk clones (sequence type 34 [ST34]) but through plasmids of various replicon types. Furthermore, the ban on colistin use in food animals can lead to a decrease in the mcr-positive Salmonella prevalence among diarrheal patients, related mainly to IncHI2A_IncHI2 plasmids. We provide a framework for plasmid data incorporation into genomic surveillance systems, contributing to a better understanding of mcr spread and transmission. IMPORTANCE Nontyphoidal Salmonella is one of four major causative agents of diarrheal diseases globally, with most cases of salmonellosis being mild. Antimicrobial treatments are required for cases of life-threatening infections, and colistin is one of the last-line antibiotics for the treatment of multidrug-resistant Salmonella infections. However, the efficacy of colistin has been compromised by the emergence of various mcr genes. To elucidate the transmission of mcr genes in Salmonella isolates, our study analyzed 7,106 Salmonella strains from 29 provinces in China from 2011 to 2020. The results showed that mcr genes are transmitted on similar high-risk clones (ST34) but through plasmids of various replicon types. In addition, our data illustrated that the ban on the use of colistin in food animals led to a significant decrease in mcr-positive isolates. Our findings offer an essential step toward a more comprehensive understanding of the spread and transmission of mcr genes.

Project description:Colistin is one of the last-resort antibiotics for infections caused by multidrug-resistant Gram-negative bacteria. However, the wide spread of novel plasmid-carrying colistin resistance genes mcr-1 and its variants substantially compromise colistin's therapeutic effectiveness and pose a severe danger to public health. To detect colistin-resistant microorganisms induced by mcr genes, rapid and reliable antibiotic susceptibility testing (AST) is imminently needed. In this study, we identified an RNA-based AST (RBAST) to discriminate between colistin-susceptible and mcr-1-mediated colistin-resistant bacteria. After short-time colistin treatment, RBAST can detect differentially expressed RNA biomarkers in bacteria. Those candidate mRNA biomarkers were successfully verified within colistin exposure temporal shifts, concentration shifts, and other mcr-1 variants. Furthermore, a group of clinical strains were effectively distinguished by using the RBAST approach during the 3-h test duration with over 93% accuracy. Taken together, our findings imply that certain mRNA transcripts produced in response to colistin treatment might be useful indicators for the development of fast AST for mcr-positive bacteria. IMPORTANCE The emergence and prevalence of mcr-1 and its variants in humans, animals, and the environment pose a global public health threat. There is a pressing urgency to develop rapid and accurate methods to identify MCR-positive colistin-resistant bacteria in the clinical samples, providing a basis for subsequent effective antibiotic treatment. Using the specific mRNA signatures, we develop an RNA-based antibiotic susceptibility testing (RBAST) for effectively distinguishing colistin-susceptible and mcr-1-mediated colistin-resistant strains. Meanwhile, the detection efficiency of these RNA biomarkers was evidenced in other mcr variants-carrying strains. By comparing with the traditional AST method, the RBAST method was verified to successfully characterize a set of clinical isolates during 3 h assay time with over 93% accuracy. Our study provides a feasible method for the rapid detection of colistin-resistant strains in clinical practice.

Project description:Antibiotic resistance is a prevalent problem in public health worldwide. In general, the carbapenem β-lactam antibiotics are considered a final resort against lethal infections by multidrug-resistant bacteria. Colistin is a cationic polypeptide antibiotic and acts as the last line of defense for treatment of carbapenem-resistant bacteria. Very recently, a new plasmid-borne colistin resistance gene, mcr-2, was revealed soon after the discovery of the paradigm gene mcr-1, which has disseminated globally. However, the molecular mechanisms for MCR-2 colistin resistance are poorly understood. Here we show a unique transposon unit that facilitates the acquisition and transfer of mcr-2 Evolutionary analyses suggested that both MCR-2 and MCR-1 might be traced to their cousin phosphoethanolamine (PEA) lipid A transferase from a known polymyxin producer, Paenibacillus Transcriptional analyses showed that the level of mcr-2 transcripts is relatively higher than that of mcr-1 Genetic deletions revealed that the transmembrane regions (TM1 and TM2) of both MCR-1 and MCR-2 are critical for their location and function in bacterial periplasm, and domain swapping indicated that the TM2 is more efficient than TM1. Matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) confirmed that all four MCR proteins (MCR-1, MCR-2, and two chimeric versions [TM1-MCR-2 and TM2-MCR-1]) can catalyze chemical modification of lipid A moiety anchored on lipopolysaccharide (LPS) with the addition of phosphoethanolamine to the phosphate group at the 4' position of the sugar. Structure-guided site-directed mutagenesis defined an essential 6-residue-requiring zinc-binding/catalytic motif for MCR-2 colistin resistance. The results further our mechanistic understanding of transferable colistin resistance, providing clues to improve clinical therapeutics targeting severe infections by MCR-2-containing pathogens.IMPORTANCE Carbapenem and colistin are the last line of refuge in fighting multidrug-resistant Gram-negative pathogens. MCR-2 is a newly emerging variant of the mobilized colistin resistance protein MCR-1, posing a potential challenge to public health. Here we report transfer of the mcr-2 gene by a unique transposal event and its possible origin. Distribution of MCR-2 in bacterial periplasm is proposed to be a prerequisite for its role in the context of biochemistry and the colistin resistance. We also define the genetic requirement of a zinc-binding/catalytic motif for MCR-2 colistin resistance. This represents a glimpse of transferable colistin resistance by MCR-2.

Dataset Information

Occurrence of mcr-mediated colistin resistance in Salmonella clinical isolates in Thailand.

Publications

Occurrence of mcr-mediated colistin resistance in Salmonella clinical isolates in Thailand.

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