Characterization of the global distribution and diversified plasmid reservoirs of the colistin resistance gene mcr-9

Abstract

The emergence and spread of mobilized colistin resistance (mcr) genes have triggered extensive concerns worldwide. Here, we characterized the global distribution of mcr-9, a newly-identified variant of mcr, by assembling the data set of mcr-9-positive isolates from GenBank database and the literature available. Genetic features of all the mcr-9-harboring plasmids were determined by bioinformatic analysis. We showed that mcr-9 is globally distributed in 21 countries across six continents, with a wide dissemination among various species of Enterobacteriaceae strains from human, animal, food and environment. IncHI2-ST1 plasmids were found to be the predominant replicon type carrying mcr-9. Comparative genomics highlighted that IncHI2-type plasmids may also serve as a critical reservoir of mcr-9, from which different types of circulating plasmids acquired the mcr-9. Results revealed that the rcnR-rcnA-pcoE-pcoS-IS903-mcr-9-wbuC structure was consistent in most mcr-9 cassettes, suggesting a relatively unitary model involved in the mobilization of mcr-9. It is most likely that the spread of mcr-9 was mainly attributed to the conjugation and recombination events of mcr-9-carrying plasmids. In summary, our results provide a comprehensive picture of the distribution and genetic environment of mcr-9, and demonstrate the central roles played by IncHI2 plasmids in the worldwide dissemination of mcr-9. Antibiotic resistance poses a great threat to global public health and carbapenem-resistant Enterobacteriaceae is triggering a health crisis worldwide 1,2. Colistin, a cationic cyclic-peptide, is one of the last-resort antibiotics to defend against severe infections caused by carbapenem-resistant Enterobacteriaceae 3. However, since the initial discovery of a plasmid-mediated mobilized colistin resistance gene (mcr-1) in China in late 2015 4 , a number of diversified bacterial strains carrying mcr-1 have been detected across over 50 countries covering six continents 5. The prevalent plasmid-borne MCR enzyme can catalyze chemical addition of phosphoethanolamine to lipid A moiety of bacterial lipopolysaccharides, the target of colistin, which consequently promotes colistin resistance 6. In recent years, a growing number of mcr-like genes (namely, from mcr-2 to mcr-10) have been identified 7-14. These ongoing discoveries indicate a rapid evolution of MCR family under selective pressures, which raise global health concerns. mcr-9 is a newly emerging variant of the mobilized colistin resistance determinants, which was first identified in a clinical Salmonella enterica isolate in the USA in May, 2019 13. Since its initial identification, mcr-9 has been reported in several other countries, such as China 15 , Sweden 16 , and France 17. Not only that, in silico analysis using the GenBank database indicated that mcr-9 had already been presented in a number of Enterobacteriaceae isolates recovered worldwide 13,17. The high prevalence of mcr-9 suggests one more threat to public health. However, little information is available about the glo...

Characterization of a Clinical Enterobacter hormaechei Strain Belonging to Epidemic Clone ST418 Co-carrying blaNDM-1, blaIMP-4 and mcr-9.1

“…1). Consistently, a recent report identi ed that IncHI2-type plasmids may serve as a critical reservoir of mcr-9 (22). Blasting the sequence of pECL-90-2 in GenBank database showed the best matches were plasmid pGW1 carried by a Cronobacter sakazakii strain GZcsf-1 (CP028975, 86.8% query coverage and 99.99% sequence identity) and plasmid p17277A_477 carried by a Klebsiella quasipneumoniae subsp.…”

“…This is consistent with the previous report that mcr − 9.1 is inactive in colistin resistance (21). A recent study with global data revealed that Enterobacter spp., was the predominant host of mcr-9 (37%) (22).…”

Genomic Insights of Multidrug-Resistant Escherichia coli From Wastewater Sources and Their Association With Clinical Pathogens in South Africa

“…The mcr-9 gene was first reported in a clinical Salmonella Typhimurium isolate in the USA in May 2019 (24). Isolates harboring mcr-9 were subsequently identified in 21 countries covering six continents, including Europe, Asia, America, Oceania, South America, and Africa (27). An mcr-9 harboring Enterobacter hormaechei isolate obtained from the sputum of a patient in Cairo, Egypt, is to date the only mcr-9 positive isolate reported in Africa (28).…”

Detection of Five mcr-9 -Carrying Enterobacterales Isolates in Four Czech Hospitals

“…Following the first description, several reports describing the presence of mcr-1 in different host species and geographic areas were published ( 7 , 8 ). Thus far, the mcr gene family comprises mcr-1 to mcr-10 ( 9 ). These genes encode phosphoethanolamine transferases that catalyze the addition of phosphoethanolamine to the phosphate group of lipid A, reducing the negative charge of the bacterial outer membrane and attenuating its affinity for colistin, resulting in antibiotic resistance.…”

“…The mcr-9 gene has been identified from 40 countries across six continents. However, half of mcr-9 -positive isolates (1,035/1,682 strains) were recovered in the United States, among which Salmonella enterica was the most common host species, especially in turkeys and chickens ( 9 ).…”