Dataset Information

Occurrence and Characteristics of Mobile Colistin Resistance (mcr) Gene-Containing Isolates from the Environment: A Review.

ABSTRACT: The emergence and spread of mobile colistin (COL) resistance (mcr) genes jeopardize the efficacy of COL, a last resort antibiotic for treating deadly infections. COL has been used in livestock for decades globally. Bacteria have mobilized mcr genes (mcr-1 to mcr-9). Mcr-gene-containing bacteria (MGCB) have disseminated by horizontal/lateral transfer into diverse ecosystems, including aquatic, soil, botanical, wildlife, animal environment, and public places. The mcr-1, mcr-2, mcr-3, mcr-5, mcr-7, and mcr-8 have been detected in isolates from and/or directly in environmental samples. These genes are harboured by Escherichia coli, Enterobacter, Klebsiella, Proteus, Salmonella, Citrobacter, Pseudomonas, Acinetobacter, Kluyvera, Aeromonas, Providencia, and Raulotella isolates. Different conjugative and non-conjugative plasmids form the backbones for mcr in these isolates, but mcr have also been integrated into the chromosome of some strains. Insertion sequences (IS) (especially ISApl1) located upstream or downstream of mcr, class 1-3 integrons, and transposons are other drivers of mcr in the environment. Genes encoding multi-/extensive-drug resistance and virulence are often co-located with mcr on plasmids in environmental isolates. Transmission of mcr to/among environmental strains is clonally unrestricted. Contact with the mcr-containing reservoirs, consumption of contaminated animal-/plant-based foods or water, international animal-/plant-based food trades and travel, are routes for transmission of MGCB.

SUBMITTER: Anyanwu MU

PROVIDER: S-EPMC7036836 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

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Occurrence and Characteristics of Mobile Colistin Resistance (mcr) Gene-Containing Isolates from the Environment: A Review.

Anyanwu Madubuike Umunna MU Jaja Ishmael Festus IF Nwobi Obichukwu Chisom OC

International journal of environmental research and public health 20200206 3

The emergence and spread of mobile colistin (COL) resistance (mcr) genes jeopardize the efficacy of COL, a last resort antibiotic for treating deadly infections. COL has been used in livestock for decades globally. Bacteria have mobilized mcr genes (mcr-1 to mcr-9). Mcr-gene-containing bacteria (MGCB) have disseminated by horizontal/lateral transfer into diverse ecosystems, including aquatic, soil, botanical, wildlife, animal environment, and public places. The mcr ...[more]

PMID: 32041167

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Project description:Mobile colistin resistance (mcr) genes (mcr-1 to mcr-10) are plasmid-encoded genes that threaten the clinical utility of colistin (COL), one of the highest-priority critically important antibiotics (HP-CIAs) used to treat infections caused by multidrug-resistant and extensively drug-resistant bacteria in humans and animals. For more than six decades, COL has been used largely unregulated in the poultry sector in low- and middle-income countries (LMICs), and this has led to the development/spread of mcr gene-containing bacteria (MGCB). The prevalence rates of mcr-positive organisms from the poultry sector in LMICs between January 1970 and May 2023 range between 0.51% and 58.8%. Through horizontal gene transfer, conjugative plasmids possessing insertion sequences (ISs) (especially ISApl1), transposons (predominantly Tn6330), and integrons have enhanced the spread of mcr-1, mcr-2, mcr-3, mcr-4, mcr-5, mcr-7, mcr-8, mcr-9, and mcr-10 in the poultry sector in LMICs. These genes are harboured by Escherichia, Klebsiella, Proteus, Salmonella, Cronobacter, Citrobacter, Enterobacter, Shigella, Providencia, Aeromonas, Raoultella, Pseudomonas, and Acinetobacter species, belonging to diverse clones. The mcr-1, mcr-3, and mcr-10 genes have also been integrated into the chromosomes of these bacteria and are mobilizable by ISs and integrative conjugative elements. These bacteria often coexpress mcr with virulence genes and other genes conferring resistance to HP-CIAs, such as extended-spectrum cephalosporins, carbapenems, fosfomycin, fluoroquinolone, and tigecycline. The transmission routes and dynamics of MGCB from the poultry sector in LMICs within the One Health triad include contact with poultry birds, feed/drinking water, manure, poultry farmers and their farm workwear, farming equipment, the consumption and sale of contaminated poultry meat/egg and associated products, etc. The use of pre/probiotics and other non-antimicrobial alternatives in the raising of birds, the judicious use of non-critically important antibiotics for therapy, the banning of nontherapeutic COL use, improved vaccination, biosecurity, hand hygiene and sanitization, the development of rapid diagnostic test kits, and the intensified surveillance of mcr genes, among others, could effectively control the spread of MGCB from the poultry sector in LMICs.

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 and Characteristics of Mobile Colistin Resistance (mcr) Gene-Containing Isolates from the Environment: A Review.

Publications

Occurrence and Characteristics of Mobile Colistin Resistance (<i>mcr</i>) Gene-Containing Isolates from the Environment: A Review.

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