Multidrug resistance in Escherichia coli has become a worrying issue that is increasingly observed in human but also in veterinary medicine worldwide. E. coli is intrinsically susceptible to almost all clinically relevant antimicrobial agents, but this bacterial species has a great capacity to accumulate resistance genes, mostly through horizontal gene transfer. The most problematic mechanisms in E. coli correspond to the acquisition of genes coding for extended-spectrum β-lactamases (conferring resistance to broad-spectrum cephalosporins), carbapenemases (conferring resistance to carbapenems), 16S rRNA methylases (conferring pan-resistance to aminoglycosides), plasmid-mediated quinolone resistance (PMQR) genes (conferring resistance to [fluoro]quinolones), and mcr genes (conferring resistance to polymyxins). Although the spread of carbapenemase genes has been mainly recognized in the human sector but poorly recognized in animals, colistin resistance in E. coli seems rather to be related to the use of colistin in veterinary medicine on a global scale. For the other resistance traits, their cross-transfer between the human and animal sectors still remains controversial even though genomic investigations indicate that extended-spectrum β-lactamase producers encountered in animals are distinct from those affecting humans. In addition, E. coli of animal origin often also show resistances to other-mostly older-antimicrobial agents, including tetracyclines, phenicols, sulfonamides, trimethoprim, and fosfomycin. Plasmids, especially multiresistance plasmids, but also other mobile genetic elements, such as transposons and gene cassettes in class 1 and class 2 integrons, seem to play a major role in the dissemination of resistance genes. Of note, coselection and persistence of resistances to critically important antimicrobial agents in human medicine also occurs through the massive use of antimicrobial agents in veterinary medicine, such as tetracyclines or sulfonamides, as long as all those determinants are located on the same genetic elements.

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Antimicrobial resistance in Escherichia coli.

Colistin is an old antimicrobial that has been revitalized as last-resort treatment against multidrug-resistant (MDR) gram-negative bacterial infections. However, colistin has been widely used in agricultural production and veterinary medicine for decades, and the recent global dissemination of mobilized colistin resistance (mcr) genes from animals to humans seriously threats the clinical use of colistin. Most of the mcr-harboring isolates have been Enterobacteriaceae, such as Escherichia coli and Salmonella enterica which are common to animals and humans. An understanding of the origin, dissemination and transmission of mcr genes in bacteria common to animals and humans will facilitate the management of colistin use and relevant interventions to prevent further spread of resistance. This review aims to provide a comprehensive assessment of the global prevalence and transmission of mcr genes of animal and human commensal/pathogenic bacteria.

Prevalence and transmission of mobilized colistin resistance (mcr) gene in bacteria common to animals and humans

Prevalence and characteristics of multidrug-resistant mcr-1-positive Escherichia coli isolates from broiler chickens in Tai'an, China.

Silver gulls carry phylogenetically diverse Escherichia coli, including globally dominant extraintestinal pathogenic E. coli (ExPEC) sequence types and pandemic ExPEC-ST131 clades; however, our large-scale study (504 samples) on silver gulls nesting off the coast of New South Wales identified E. coli ST457 as the most prevalent. A phylogenetic analysis of whole-genome sequences (WGS) of 138 ST457 samples comprising 42 from gulls, 2 from humans (Australia), and 14 from poultry farmed in Paraguay were compared with 80 WGS deposited in public databases from diverse sources and countries. E. coli ST457 strains are phylogenetic group F, carry fimH145, and partition into five main clades in accordance to predominant flagella H-antigen carriage. Although we identified considerable phylogenetic diversity among the 138 ST457 strains, closely related subclades (<100 SNPs) suggested zoonotic or zooanthroponosis transmission between humans, wild birds, and food-producing animals. Australian human clinical and gull strains in two of the clades were closely related (≤80 SNPs). Regarding plasmid content, country, or country/ source, specific connections were observed, including I1/ST23, I1/ST314, and I1/ ST315 disseminating bla in Australia, I1/ST113 carrying bla and mcr-5 in Paraguayan poultry, and F2:A-:B1 plasmids of Dutch origin being detected across multiple ST457 clades. We identified a high prevalence of nearly identical I1/ST23 plasmids carrying bla among Australian gull and clinical human strains. In summary, ST457 is a broad host range, geographically diverse E. coli lineage that can cause human extraintestinal disease, including urinary tract infection, and displays a remarkable ability to capture mobile elements that carry and transmit genes encoding resistance to critically important antibiotics.

Escherichia coli Sequence Type 457 Is an Emerging Extended-Spectrum-β-Lactam-Resistant Lineage with Reservoirs in Wildlife and Food-Producing Animals.

Updates on the global dissemination of colistin-resistant Escherichia coli: An emerging threat to public health

Our aim in this report was to describe the characteristics of the first clinical isolate of Escherichia coli (EC-PAG-733) harboring the mcr-1 gene found in Mexico. This isolate was obtained from a fecal sample from a young child with an oncological condition. We obtained the whole-genome sequence using next-generation sequencing and analyzed the sequence by bioinformatics tools. EC-PAG-733 was resistant to third- and fourth-generation cephalosporins and was susceptible to all carbapenems and amikacin; it was also resistant to ciprofloxacin, levofloxacin, gentamicin and colistin at a minimum inhibitory concentration (MIC) of 4 μg/mL. This isolate was classified as O11:H25-ST457. EC-PAG-733 harbored an ESBL type CTX-M-55 as well as several virulence factors that have been associated with Enteroaggregative Escherichia coli (EAEC). The mcr-1 gene was located within an IncI2 plasmid. The results of this whole genome shotgun project were deposited in DDBJ/ENA/GenBank under the accession number QKXE00000000.

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First clinical isolate of Escherichia coli harboring mcr-1 gene in Mexico.

Cytochrome P450s from the CYP52 family participate in the assimilation of alkanes and fatty acids in fungi In this work, the evolutionary history of a set of orthologous and paralogous CYP52 proteins from Saccharomycetales yeasts was inferred Further, the phenotypic assimilation profiles were related with the distribution of cytochrome CYP52 members among species The maximum likelihood phylogeny of CYP52 inferred proteins reveled a frequent ancient and modern duplication and loss events that generated orthologous and paralogous groups Phylogeny and assimilation profiles of alkanes and fatty acids showed a family expansion in yeast isolated from hydrophobic-rich environments Docking analysis of deduced ancient CYP52 proteins suggests that the most ancient function was the oxidation of C4-C11 alkanes, while the oxidation of >10 carbon alkanes and fatty acids is a derived character The ancient CYP52 paralogs displayed partial specialization and promiscuous interaction with hydrophobic substrates Additionally, functional optimization was not evident Changes in the interaction of ancient CYP52 with different alkanes and fatty acids could be associated with modifications in spatial orientations of the amino acid residues that comprise the active site The extended family of CYP52 proteins is likely evolving toward functional specialization, and certain redundancy for substrates is being maintained

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Jazmin Murcia-Garzón

Papers

First clinical isolate of Escherichia coli harboring mcr-1 gene in Mexico.

Phylogeny, evolution, and potential ecological relationship of cytochrome CYP52 enzymes in Saccharomycetales yeasts.

Promiscuous Domains in Eukaryotes and HAT Proteins in FUNGI Have Followed Different Evolutionary Paths

Promiscuous Domains in Eukaryotes and HAT Proteins in FUNGI Have Followed Different Evolutionary Paths