Dynamics of mcr-1 prevalence and mcr-1-positive Escherichia coli after the cessation of colistin use as a feed additive for animals in China: a prospective cross-sectional and whole genome sequencing-based molecular epidemiological study

Abstract

Background The global dissemination of colistin resistance encoded by mcr-1 has been attributed to extensive use of colistin in livestock, threatening colistin efficacy in medicine. The emergence of mcr-1 in common pathogens, such as Escherichia coli, is of particular concern. China banned the use of colistin in animal feed from May 1, 2017. We investigated subsequent changes in mcr-1 prevalence in animals, humans, food, and the environment, and the genomic epidemiology of mcr-1-positive E coli (MCRPEC).Methods Sampling was done before (October to December, 2016) and after (October to December, 2017, and 2018, respectively) the colistin ban. 3675 non-duplicate pig faecal samples were collected from 14 provinces (66 farms) in China to measure intervention-related changes in mcr-1 prevalence. 15 193 samples were collected from pigs, healthy human volunteers, patients colonised or infected with Enterobacteriaceae who were admitted to hospital, food and the environment in Guangzhou, to characterise source-specific mcr-1 prevalence and the wider ecological effect of the ban. From these samples, 688 MCRPEC were analysed with whole genome sequencing, plasmid conjugation, and S1 pulsed-field gel electrophoresis with Southern blots to characterise associated genomic changes. FindingsAfter the ban, mcr-1 prevalence decreased significantly in national pig farms, from 308 (45%) of 684 samples in 2016 to 274 (19%) of 1416 samples in 2018 (p<0•0001). A similar decrease occurred in samples from most sources in Guangzhou (959 [19%] of 5003 samples in 2016; 238 [5%] of 4489 samples in 2018; p<0•0001). The population structure of MCRPEC was diverse (23 sequence clusters); sequence type 10 clonal complex isolates were predominant (247 [36%] of 688). MCRPEC causing infection in patients admitted to hospital were genetically more distinct and appeared less affected by the ban. mcr-1 was predominantly found on plasmids (632 [92%] of 688). Common mcr-1 plasmid types included IncX4, IncI2, and IncHI2 (502 [76%] of 656); significant increases in IncI2-associated mcr-1 and a distinct lineage of mcr-1-associated IncHI2 were observed post ban. Changes in the frequency of mcr-1-associated flanking sequences (ISApl1-negative MCRPEC), 63 core genome single nucleotide polymorphisms, and 30 accessory genes were also significantly different after the ban (Benjamini-Hochberg-adjusted p<0•05), consistent with rapid genetic adaptation in response to changing selection pressures. Interpretation A rapid, ecosystem-wide, decline in mcr-1 was observed after the use of colistin in animal feed was banned, with associated genetic changes in MCRPEC. Withdrawal of antimicrobials from animal feed should be an important One Health measure contributing to the wider control of antimicrobial resistance globally.

Widespread Prevalence of Plasmid-Mediated Colistin Resistance Gene mcr-1 in Escherichia coli from Père David's Deer in China

“…As a result, China banned the use of colistin as a feed additive for animals on 1 May 2017 ( 13 ). It has been reported that the mcr-1 prevalence decreased significantly in national pig farms after the ban of colistin in animal feed ( 14 ). A reduction in the mcr-1 -positive E. coli population size following the colistin ban could also be expected in Père David’s deer, which warrants further surveillance.…”

Genomic patterns and characterizations of chromosomally-encoded mcr-1 in Escherichia coli populations

“…Accumulated evidence showed that banning of colistin in animal feed efficiently restricted mcr-1 prevalence, not only in animals but also in humans and the whole ecosystem in China [2][3][4]. However, our previous study showed that a low proportion of Escherichia coli carrying chromosomally-encoded mcr-1 continually existed in the ecosystem [4], which was sporadically reported by other studies as well [9][10][11]. On account of the plasmid that could be lost under certain circumstances due to instability, the chromosomally-encoded events could stabilize the heritage of mcr-1, threatening the intervention of colistin stewardship.…”

“…The emergence and rapid dissemination of plasmid-mediated mobile colistin resistance gene ( mcr - 1 ) have become a severe threat to public health [ 1 ]. The predominant carriers of mcr - 1 were IncX4, IncI2, and IncHI2 plasmids, which are transferable and adaptive plasmid types with broad host range and contributed to the spread of mcr - 1 among various sources and bacterial species [ 2 – 4 ]. Besides, recombination of transposons, especially Tn 6330 (IS Apl1 - mcr - 1 - pap2 -IS Apl1 ), the primary vehicle for transmission of mcr - 1 , and phage-like sequences enable mcr - 1 to transfer across plasmids and isolates.…”

“…Accumulated evidence showed that banning of colistin in animal feed efficiently restricted mcr - 1 prevalence, not only in animals but also in humans and the whole ecosystem in China [ 2 – 4 ]. However, our previous study showed that a low proportion of Escherichia coli carrying chromosomally-encoded mcr - 1 continually existed in the ecosystem [ 4 ], which was sporadically reported by other studies as well [ 9 – 11 ].…”

First Identification of a Patient with Prosthesis-Related Infection Caused by an MCR-1.1-Producing ST131 Escherichia coli After Rhinoplasty

“…The latest research showed that the mcr-1 prevalence has been dramatically decreased to a low prevalence. 36 The rational use of antimicrobials should be considered as a key measure to prevent the rising of antimicrobial resistance.…”