Massive analysis of 64’628 bacterial genomes to decipher a water reservoir and origin of mobile colistin resistance (mcr) gene variants: is there another role for this family of enzymes?

Abstract

20Since 2015, new worrying colistin resistance mechanism, mediated by mcr-1 21 gene has been reported worldwide along with eight newly described variants (mcr-2 to mcr-9) 22 but their source(s) and reservoir(s) remain largely unexplored. Here, we conducted a massive 23 bioinformatic analysis of 64'628 downloaded bacterial genomes to investigate the reservoir 24 and origin of these mcr variants. We identified a total of 6'651 significant positive hits (aa 25 sequence coverage > 90 % and similarity >50%) with the nine MCR variants from these 26 genomes that include 39 bacterial genera and more than 1050 species. Although these variants 27 could be identified in bacteria from human and animal sources, we found plenty MCR 28 variants in unsuspected bacteria from environmental origin, especially from water sources. 29The ubiquitous presence of mcr variants in bacteria from water likely suggests another role in 30 the biosphere of these enzymes as an unknown defense system against natural antimicrobial 31 peptides and/or bacteriophage predation. 32 21.Ling, Z. et al. Chromosome-mediated mcr-3 variants in aeromonas veronii from chicken meat. 440Antimicrob. Agents Chemother. 61, (2017). 441 22. Huang, M. et al. Action and mechanism of the colistin resistance enzyme MCR-4. Commun. 442 Biol. 2, (2019).443 23. Carroll, L. M. et al. Identification of Novel Mobilized Colistin Resistance Gene mcr-9 in a 595Suppl. Figure S2. Phylogenetic tree performed from MCR variant hits (n=6'648 proteins) with aa identity between 50% and 100% and 596 alignment ≥ 90%. 597

Characterization of Extended-Spectrum Beta-Lactamase-Producing Escherichia coli Isolates from Jurong Lake, Singapore with Whole-Genome-Sequencing

“…However, as the functions of the protein in the WbuC family were highly varied in different species, the role of it here with bla CTX-M-15 is still not well documented. The resistance genes in this unique gene cluster are not limited to bla CTX-M, and mcr-9 has also been reported to be followed by WbuC genes recently [29]. Therefore, the functional studies of the WbuC genes will be very interesting in the future.…”

Comparison of Antimicrobial Resistance Detected in Environmental and Clinical Isolates from Historical Data for the US

“…For example, although fosA7 was detected in more environmental isolates in this study, it was also detected in human clinical cases. Since this work is aimed at identifying genes mostly involved in antimicrobial resistance, instead of providing thorough investigation of the functions of those genes, a brief introduction of each of the aforementioned genes is given in Figure 3 [22][23][24][25][26][27][28][29][30][31][32][33][34][35]. All AMR genes listed in Figure 3 were further analyzed with their historical occurrence profiles.…”

“…Fosfomycin resistance glutathione transferase [26] mcr-9.1 Mobile colistin resistance unsuspected bacteria from environmental origin [27] aadA1 Aminoglycoside 3''-adenylyltransferase [28] aadA2…”

Molecular epidemiology of mcr gene group

“…В мета исследовании Khedher M. и соавт. было показано, что все варианты генов mcr имеют происхождение из ДНК бактерий окружающей среды, причем их природным ре зервуаром являются в основном сточные воды [132]. Учитывая, что гены резистентности mcr, вероятно, могут переносится как в составе плазмиды, так и посредствам транспозона [133], можно предположить, что чрезвы чайно широкое распространение в природе таких де терминант неизбежно приведет к появлению новых ва риантов генов mcr.…”

“…В настоящее время 60% случаев выявления генетичес ких детерминант устойчивости к колистину mcr в России приходится на нозокомиальные штаммы, причем боль шинство штаммов было получено из Сибирского феде рального округа [45]. В связи с тем что природными резервуарами mcr являются в основном распространен ные в окружающей среде бактерии [132], а также при нимая во внимание недавние исследования, показываю щие возможность переноса генов mcr перелетными птицами [78], можно предположить, что появление ге нов mcr в России обусловлено территориальной близо стью к месту первого обнаружения [6] генов мобильной резистентности к колистину.…”