<p>Characterization Of Chromosome-Mediated Colistin Resistance In <em>Escherichia coli</em> Isolates From Livestock In Korea</p>

Abstract

PurposeColistin resistance in gram-negative bacteria from humans and livestock has been increasingly reported worldwide. The aim of this study was to investigate the underlying mechanisms of chromosome-mediated colistin resistance in Escherichia coli isolates from livestock in Korea.Materials and methodsThirty mcr-1-negative isolates were selected from a collection of colistin-resistant E. coli isolates collected from livestock in 2005 and 2015 in Korea. Amino acid alterations in PmrAB, PhoPQ, MgrB, and PmrD were investigated. Colistin-resistant derivatives were produced by serial passage of colistin-susceptible E. coli isolates in colistin-containing media.ResultsThirty colistin-resistant mcr-negative E. coli isolates were classified into 26 sequence types. Twenty-two isolates carried diverse amino acid alterations in PmrB, PhoP, PhoQ, MgrB, and/or PmrD, whereas no mutation in any of these genes was found in the remaining eight isolates. Sixteen out of the 22 isolates shared a total of nine polymorphic positions that were found in colistin-susceptible E. coli strains. Colistin-resistant derivatives from two colistin-susceptible isolates showed the same genetic alterations that were observed in colistin-resistant clinical isolates.ConclusionOur results suggest that the mechanism underlying chromosome-mediated colistin resistance remain to be discovered in E. coli. Selective pressure of colistin in vitro induced the same genetic mutations associated with colistin resistance in vivo. Efforts to reduce colistin consumption in livestock should be redoubled, to prevent the occurrence of colistin-resistant E. coli strains.

Genomic Insights into a Colistin-Resistant Uropathogenic Escherichia coli Strain of O23:H4-ST641 Lineage Harboring mcr-1.1 on a Conjugative IncHI2 Plasmid from Egypt

“…These modifications are associated with mutations inthe two-component systems PhoP/PhoQ and PmrA/PmrB [ 28 ]. Mutations in mgrB and pmrD genes are also known to play a role in colistin resistance in the Enterobacteriaceae , where the inactivation of MgrB, the negative regulator of the PhoPQ system, leads to overexpression of the phoPQ operon, whereas the activation of PmrD by PhoP upregulates PmrAB [ 15 ]. To address this part, the full nucleotide sequences of PhoP , PhoQ , pmrA , pmrB, mgrB and pmrD from the three colistin-resistant isolates were inspected and compared to those of E. coli K-12 MG1655 ( Table 3 ).…”

“…Six amino acid alterations were detected in PmrB, among which E123D and Y358N mutations, located in the histidine kinase and phosphate-related domain, might affect the phosphate transfer between the two-component systems resulting in colistin-resistant isolates [ 29 ]. PmrD, which promotes the connection of PhoPQ and PmrAB two-component systems, displayed mutations at four sites (L19I, S71C, V83A and D14N), but their associations with colistin resistance have not been reported [ 15 ]. Although the double mechanism of colistin resistance, the production of mcr-1 gene along with amino acid substitution in PmrB (E123D and Y358N) or PmrA (G144S), depicted in this study in isolates EC14142 and EC13655 is considered a rare finding, it has been reported earlier by other investigators [ 30 ].…”

“…E. coli isolates with a colistin MIC value of >2 μg/mL were screened using PCR for the presence of mobile colistin resistance genes, mcr-1 and mcr-2 [ 14 ], and the following chromosomally encoded genes related to colistin resistance: pmrA , pmrB , PhoP , PhoQ , mgrB and pmrD [ 15 ]. Other plasmid-borne genes conferring resistance to extended-spectrum β-lactams such as bla SHV and bla TEM [ 16 ], carbapenems, bla NDM [ 17 ], and fluoroquinolones, qnrB [ 16 ], were analyzed as well.…”

Polymyxins and Bacterial Membranes: A Review of Antibacterial Activity and Mechanisms of Resistance

“…Although mgrB mutations or inactivation were suggested as major mechanisms for colistin resistance in K. pneumoniae [ 105 , 106 , 107 ], Borsa et al reported an overexpression of PhoQ and phoP genes in K. pneumoniae with wild-type mgrB gene, suggesting that other genetic regulations of the PhoPQ system may exist [ 108 ]. A very recent report from Korea described the mgrB alteration mediating colistin resistance in E. coli isolated from livestock [ 109 ]. It is noteworthy that the mutation of genes other than mgrB may contribute to enhancing PhoPQ system activity, such as ColR/ColS and CprR/CprS regulatory systems in P. aeroginosa [ 110 ], and cprR/cprS in C. jejuni [ 99 ].…”

Molecular characteristics of antibiotic-resistant Escherichia coli and Klebsiella pneumoniae strains isolated from hospitalized patients in Tehran, Iran

“…The recent increase in the use of colistin in clinical practice, accompanied by its unbridled use in agriculture, have contributed to the rapid dissemination of resistance [ 14 ]. Colistin resistance is caused by decreases in the net negative charge of the outer membrane, loss of lipid A, or efflux pumps and plasmid-encoded mcr genes [ 15 ]. The mcr-1 gene uses a target site modification mechanism to protect bacteria from the action of colistin.…”