Definition of a Family of Nonmobile Colistin Resistance (NMCR‐1) Determinants Suggests Aquatic Reservoirs for MCR‐4

Zhang, Huimin; Wei, Wenhui; Huang, Man; Umar, Zeeshan; Feng, Youjun

doi:10.1002/advs.201900038

Cited by 33 publications

(28 citation statements)

References 90 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Similar to previous studies ( Denervaud Tendon et al, 2017 ; Yang et al, 2017 ; Zhang et al, 2019 ), we found that the expression of mcr-1 was orchestrated and associated with an initial fitness cost (reduced growth at 8 h). However, to the best of our knowledge our study is the first to examine in any bacterial species the impact of the over-expression of the mcr-1 on bacterial metabolism.…”

Section: Discussionsupporting

confidence: 90%

Metabolic Perturbations Caused by the Over-Expression of mcr-1 in Escherichia coli

et al. 2020

View full text Add to dashboard Cite

Rapid dissemination of the plasmid-born polymyxin resistance gene mcr-1 poses a critical medical challenge. MCR-1 expression is tightly controlled and imposes a fitness cost on the bacteria. We used growth studies and metabolomics to examine growth and metabolic changes within E. coli TOP10 at 8 and 24 h in response to different levels of expression of mcr-1 . Induction of mcr-1 greatly increased expression at 8 h and markedly reduced bacterial growth; membrane disruption and cell lysis were evident at this time. At 24 h, the expression of mcr-1 dramatically declined with restored growth and membrane integrity, indicating regulation of mcr-1 expression in bacteria to maintain membrane homeostasis. Intermediates of peptide and lipid biosynthesis were the most commonly affected metabolites when mcr-1 was overexpressed in E. coli . Cell wall biosynthesis was dramatically affected with the accumulation of lipids including fatty acids, glycerophospholipids and lysophosphatidylethanolamines, especially at 8 h. In contrast, levels of intermediate metabolites of peptides, amino sugars, carbohydrates and nucleotide metabolism and secondary metabolites significantly decreased. Moreover, the over-expression of mcr-1 resulted in a prolonged reduction in intermediates associated with pentose phosphate pathway and pantothenate and CoA biosynthesis. These findings indicate that over-expression of mcr-1 results in global metabolic perturbations that mainly involve disruption to the bacterial membrane, pentose phosphate pathway as well as pantothenate and CoA biosynthesis.

show abstract

Section: Discussionsupporting

confidence: 90%

Metabolic Perturbations Caused by the Over-Expression of mcr-1 in Escherichia coli

et al. 2020

View full text Add to dashboard Cite

show abstract

“…MCR-3 was reported from Aeromonas species isolated from river water 32 . It has recently been reported that the aquatic bacteria of the genus Shewanella are a reservoir/progenitor for mcr-4 encoding gene 41 . MCR-5 and MCR-8 were described from the same Stenotrophomonas strain isolated from sewage water in China 30 .…”

Section: Discussionmentioning

confidence: 99%

Massive analysis of 64,628 bacterial genomes to decipher water reservoir and origin of mobile colistin resistance genes: is there another role for these enzymes?

Khedher

Baron

Riziki

et al. 2020

Sci Rep

View full text Add to dashboard Cite

Since 2015, new worrying colistin resistance mechanism, mediated by mcr-1 gene has been reported worldwide along with eight newly described variants but their source(s) and reservoir(s) remain largely unexplored. Here, we conducted a massive bioinformatic analysis of bacterial genomes to investigate the reservoir and origin of mcr variants. We identified 13'658 MCR-1 homologous sequences in 494 bacterial genera. Moreover, analysis of 64'628 bacterial genomes (60 bacterial genera and 1'047 species) allows identifying a total of 6'651 significant positive hits (coverage >90% and similarity >50%) with the nine MCR variants from 39 bacterial genera and more than 1'050 species. A high number of MCR-1 was identified in Escherichia coli (n = 862). Interestingly, while almost all variants were identified in bacteria from different sources (i.e. human, animal, and environment), the last variant, MCR-9, was exclusively detected in bacteria from human. Although these variants could be identified in bacteria from human and animal sources, we found plenty MCR variants in unsuspected bacteria from environmental origin, especially from water sources. The ubiquitous presence of mcr variants in bacteria from water likely suggests another role in the biosphere of these enzymes as an unknown defense system against natural antimicrobial peptides and/or bacteriophage predation.

show abstract

“…Accordingly, the United Nations Environment Programme (UNEP) recently identified environmental AMR as the top six emerging issues of concern [25,26]. In One Health model, surveillance of ARGs in humans, animals, soil, plant, aquatic and aquaculture environment is crucial in determining the extent of dissemination of a targeted ARG [2,27]. Potentially pathogenic COLROS emanating from any of these ecosystems can move with relative ease to another without barriers [2,25].…”

Section: Introductionmentioning

confidence: 99%

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

Anyanwu

Jaja

Nwobi

2020

IJERPH

102

112

View full text Add to dashboard Cite

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.

show abstract

Definition of a Family of Nonmobile Colistin Resistance (NMCR‐1) Determinants Suggests Aquatic Reservoirs for MCR‐4

Cited by 33 publications

References 90 publications

Metabolic Perturbations Caused by the Over-Expression of mcr-1 in Escherichia coli

Metabolic Perturbations Caused by the Over-Expression of mcr-1 in Escherichia coli

Massive analysis of 64,628 bacterial genomes to decipher water reservoir and origin of mobile colistin resistance genes: is there another role for these enzymes?

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

Contact Info

Product

Resources

About