Action and mechanism of the colistin resistance enzyme MCR-4

Zhang, Huimin; Hou, Mengyun; Xu, Yongchang; Srinivas, Swaminath; Huang, Man; Liu, Lizhang; Feng, Youjun

doi:10.1038/s42003-018-0278-1

Cited by 60 publications

(78 citation statements)

References 73 publications

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“…According to the other two studies, mcr-4.3 alone did not confer phenotypic resistance to colistin (14) and showed a lack of lipid A modification function (15). Recently, a study on the action and mechanism of MCR-4 showed that revertants of mcr-4.3 (either V179G or V236F) led to its expression and conferred colistin resistance of 8 g/ml, together with the acquired function of lipid A modification (22).…”

Section: Resultsmentioning

confidence: 99%

Identification of a Novel Plasmid Carrying mcr-4.3 in an Acinetobacter baumannii Strain in China

Cong

Zheng

et al. 2019

Antimicrob Agents Chemother

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Here, we identified mcr-4.3 in Acinetobacter baumannii, which had not been previously observed to carry an mcr gene. The mcr-4.3-harboring A. baumannii strain AB18PR065 was isolated from pig feces from a slaughterhouse in Guangdong Province of China. The mcr-4.3-carrying pAB18PR065 is 25,602 bp in size and could not be transferred in conjugation, transformation, and electroporation experiments, as we did not find any conjugation-related genes therein. pAB18PR065 harbors two copies of type II toxin-antitoxin systems, which are functional in plasmid stabilization and maintenance. pAB18PR065 shares similarity only with one recently identified plasmid, pAb-MCR4.3 (35,502 bp), from a clinical A. baumannii strain. It is likely that the emergence of pAb-MCR4.3 was due to the insertion of an 11,386-bp, ISAba19based, composite transposon into pAB18PR065. These data indicate that mcr-4.3 was captured by an A. baumannii-original plasmid via horizontal gene transfer.

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Section: Resultsmentioning

confidence: 99%

Identification of a Novel Plasmid Carrying mcr-4.3 in an Acinetobacter baumannii Strain in China

Cong

Zheng

et al. 2019

Antimicrob Agents Chemother

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“…Unfortunately, many species of Enterobacteriaceae are becoming increasingly resistant to colistin 2,4,6,7. One colistin resistant mechanism is the modification of Lipid A of LPS, catalyzed by the chromosome encoded machinery in Klebsiella pneumoniae , the LptA (EptA) in Neisseria , or mobile colistin resistance mcr‐1 in Enterobacteriaceae 5,8–11. Since its discovery in China, mcr‐1 resistance was reported in several other countries spanning six continents 5–7,12.…”

Section: Introductionmentioning

confidence: 99%

Carriage of Distinct mcr‐1‐Harboring Plasmids by Unusual Serotypes of Salmonella

et al. 2020

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Colistin acts as a last‐resort antibiotic against lethal infections by carbapenem‐resistant Enterobacterial pathogens. Enterobacteriaceae carrying mobile colistin resistance (MCR) genes are rapidly emerging and threatening human health and food safety. Despite mcr‐1 being prevalent in Escherichia coli, its dissemination in Salmonella is not well characterized. Herein, two unusual serotypes of colistin‐resistant Salmonella isolates are reported first, namely serotype Ngor (ST5399) and Goldcoast (ST2529). Using whole genome sequencing, it is shown that mcr‐1 is located on the IncHI2‐like plasmid pTB501 (188,527 bp) of strain SSDFZ54 and the IncX4‐type plasmid pTB602 (33,303 bp) in strain SSDFZ69, respectively. Furthermore, the backbone, tra‐ and antimicrobial resistance genes relative variable regions in the mcr‐1‐bearing IncHI2 plasmids are systematically characterized. Phylogenetic analysis shows that all IncHI2‐type plasmids from non‐Chinese regions are clustered together, suggesting a possible Chinese origin. Taken together, these findings extend the understanding of Salmonella as a vehicle of mcr‐1 carriage and distribution.

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“…[6][7][8][9] MCR proteins function as phosphoethanolamine (PEA) transferases that catalyze the addition of a PEA moiety from phosphatidylethanolamine to the head group of lipid A through a ping-pong mechanism. 10,11 Modification of lipid A with PEA is thought to reduce the affinity of colistin to LPS, and thus confers bacterial resistance to the antibiotic. 11 To date, 10 mcr genes (mcr-1 to mcr-10) carried by plasmids with varied replicon types have been identified in various bacterial species.…”

Section: Introductionmentioning

confidence: 99%

Co-Occurrence of the mcr-1.1 and mcr-3.7 Genes in a Multidrug-Resistant Escherichia coli Isolate from China

Feng

Wang

et al. 2020

IDR

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A colistin-resistant Escherichia coli strain isolated from dog feces was characterized in this study. Methods and Results: A multiplex PCR assay was used to detect the presence of colistinresistant mcr genes; it was found that E. coli QDFD216 co-harbored the mcr-1 and mcr-3 genes. Whole-genome sequencing and further bioinformatics analysis revealed that E. coli QDFD216 belonged to serotype O176:H11, fimH1311 type and ST132. The resistance genes bla CTX-M-14 , mdfA, dfrA3, acrA, acrB, tolc, and sul3 were present in the chromosome. The mcr-1.1 and mcr-3.7 genes were located in two plasmids of different incompatibility groups. mcr-1.1 was carried by a IncX4-type plasmid within an typical IS26-parA-mcr-1.1-pap2 cassette, while mcr-3.7 was encoded by an IncP1-type plasmid with a genetic structure of TnAs2-mcr-3.7-dgkA-IS26. No additional antibiotic resistance genes were carried by either plasmid. Conclusion: This is the first report of an E. coli isolate co-harboring a mcr-1.1-carrying IncX4 plasmid and a mcr-3.7-carrying IncP1 plasmid. The evolution and mechanism of mcr gene coexistence need further study to assess its impact on public health.

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Action and mechanism of the colistin resistance enzyme MCR-4

Cited by 60 publications

References 73 publications

Identification of a Novel Plasmid Carrying mcr-4.3 in an Acinetobacter baumannii Strain in China

Identification of a Novel Plasmid Carrying mcr-4.3 in an Acinetobacter baumannii Strain in China

Carriage of Distinct mcr‐1‐Harboring Plasmids by Unusual Serotypes of Salmonella

<p>Co-Occurrence of the <em>mcr-1.1</em> and <em>mcr-3.7</em> Genes in a Multidrug-Resistant <em>Escherichia coli</em> Isolate from China</p>

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