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Volume 9 • Issue 3 • 1000243 Research Article Open Access Shad J Drug Metab Toxicol 2019 9:3 DOI: 10.4172/2157-7609.1000243 Mini Review Open Access Drug Metabolism Toxicology Journal of Drug Metabolism Toxicology ISSN: 2157-7609 J Drug Metab Toxicol an open access journal ISSN: 2157-7609 Corresponding author: Ahtesham Ahmad Shad Institute of Microbiology University of Agriculture Faisalabad Pakistan E mail: ahtesham.ashadyahoo. com Received November 11 2018 Accepted December 28 2018 Published January 05 2019 Citation: Shad AA 2019 MCR-1 Colistin Resistance in Escherichia coli Wildlife: A Continental Mini-reviewy. J Drug Metab Toxicol 9: 243. doi:10.4172/2157- 7609.1000243 Copyright: © 2019 Shad AA. This is an open-access article distributed under the terms of the Creative Commons Attribution License which permits unrestricted use distribution and reproduction in any medium provided the original author and source are credited. Abstract Antimicrobial resistance is one of the major leading problem and an issue for medical science in this era. Despite of being successful in treating bacterial infections and developing novel antibiotics we are unfortunately going back to pre-antibiotic era. ESBLs Cabapenemases and MCR-1 genes are the predisposing factors together in emerging the resistance. Horizontal gene transfer makes it favorable to spread resistance mechanisms at much faster rate. Antimicrobial resistance is taken as a more signifcant issue when it comes towards the resistance of bacterial strains towards our lost-resort antibiotic i.e. Colistin. Polymyxin E or colistin is an effective therapy against multi- drug resistant pathogens i.e. ESKAPE. But the discovery of MCR-1 gene has led to medical science to hands off at present. This mini-review aims to give a glance on MCR-1 gene mechanism of resistance in Escherichia coli and also plasmid profle and phenotypic characteristics of wildlife strains in continents conferring resistance to colistin. As the global transmission of resistance has accounted the wild life as one of the major culprit. MCR-1 Colistin Resistance in Escherichia coli Wildlife: A Continental Mini- review Ahtesham Ahmad Shad Institute of Microbiology University of Agriculture Faisalabad Pakistan Keywords: ESBLs MCR-1 ESKAPE Polymyxin E Introduction Antimicrobial resistance is one of the notoriously leading issue and universal threat to one health in this era. WHO and US Centers for Disease Control and Prevention are clearly stating about medical science going towards pre-antibiotic era 1.Te specifc markers of resistance ESBLs Carbapenemases and mcr-1 genes are helping in prevailing resistance among bacterial strains 2.Te discovery of plasmid mediated colistin resistance in the normal and routinely survey of China is devastating fnding to one health 1.Ten the rash of reports started globally in alarming the human and as well animals health 3.Within just three months of frst discovery in November 2015the spread of MCR-1 gene evidently supported by medical society worldwide 4.Isolation of MCR-1 gene from diferent locations and samples raised up the need to understand mechanisms underlying in spreading it globally especially samples from Humans animals and environment i.e. soil river water 34. As the colistin was the drug of choice or the drug of last-resort antibiotic in controlling the infections caused by multi-drug resistant pathogens in past i.e. ESKAPE 3.Te deteriorating power of this powerful and efective antibiotic posing by MCR-1 gene is a huge danger 5. Te focus of this mini-review is to highlight the basics of MCR-1 resistance mechanism in E. coli and we aim to describe and provide the reader with a glance on plasmid and phenotypic characteristics in E. coli of wildlife origin continents. E. coli E. coli is a straight Gram-negative rod most abundant facultative anaerobe in colon and feces. It has three antigens that are used to identify the organism in epidemiologic investigations: the O or cell wall antigen the H or fagellar and the K or capsular antigen 6. Because there are more than 150 O 50 H and 90 K antigens the various combinations results in more than 1000 antigenic types of E. coli 67. E. coli is the most common cause of urinary tract infection and sepsis it is one of the two important causes of neonatal meninigitis and the agent frequently associated with “traveler’s diarrhea” a watery diarrhea 8. E. coli has three major serotype classes O H K four phylotypes A B1 B2 D and two broad pathotypes Extraintestinal E. coli ExPEC and Diarrheagenic E. coli. Te Diarrheagenic E. coli has six distinct classes Enteropathogenic E. coli EPEC Enterohaemorrhagic E. coli EHEC Enterotoxigenic E. coli ETEC Enteroaggregative E. coli EAEC Enteroinvasive E. coli EIEC and Difusely adherent E. coli DAEC 9. MCR-1 gene discovery Te frst report of plasmid mediated colistin resistance designated as MCR-1 is from China during a routine surveillance project on antimicrobial resistance in commensal E. coli from food animals. MCR- 1 gene was isolated from a pig of E. coli strain SHP45 8. MCR-1 mechanism of resistance Previously all reported polymyxin resistance mechanisms are chromosomally mediated and involve modulation of two component regulatory systems eg pmrAB phoPQ 9. Based on sequence alignment MCR-1 should be a phosphoethanolamine transferase a member of YhjW/YjdB/YijP superfamily which catalyzes the addition of phosphoethanolamine to lipid A moiety of lipopolysaccharides LPS and therefore confers colistin resitance to its host 1011. Spreading ways or routes of MCR-1 transmission Te MCR-1 gene may undergo evolutionary changes in the animal GI tract upon prolonged usage of colistin as growth promoter. Te gene

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Citation: Shad AA 2019 MCR-1 Colistin Resistance in Escherichia coli Wildlife: A Continental Mini-reviewy. J Drug Metab Toxicol 9: 243. doi:10.4172/2157-7609.1000243 Page 2 of 3 Volume 9 • Issue 3 • 1000243 J Drug Metab Toxicol an open access journal ISSN: 2157-7609 is then transmitted to human through the food chain or direct human contact with animals as well as through contamination of the fresh and seawater system which in turn cause contamination of vegetables and seafood. Te persistence of MCR-1 in the human GI tract microfora can cause further contamination of the water systems through disposal of waste water containing human faeces. Fresh water systems outside these transmission routes remain clear of MCR-1 contamination 12. MCR-genes types discovered so far Five colistin resistance genes MCR-1 MCR-2 MCR-3 MCR-4 and MCR-5 have been described few data are available on the prevalence of MCR-genes other than mcr-1 in human samples 13.Moreover so far six diferent variants of the MCR-1 gene MCR-1.2 to MCR-1.7 which difer from each other by a single amino acid have been described in Enterobacteriaceae 14. Why wildlife is so important to analyze for MCR-1 gene Te development of bacterial resistance is a naturally occurring evolutionary mechanism of micro-organisms but the wide spread use and misuse of antibacterial agents in humans and animals has accelerated this process. MCR-1 is one of the few and clear example of the animal origin of a resistance trait that may later hit the entire human health 215. Since most emerging human diseases have come from wildlife and natural environment and wildlife is considered to a “melting pot” and dissemination route of antibacterial resistance 16. Role of wildlife in transmission of the MCR-1 gene Te use of antimicrobials in veterinary medicine creates a selective pressure for the emergence of antimicrobial resistant bacteria including animal human pathogens that have animal reservoirs and commensal bacteria from animals bacteria selected by this pressure can spread to humans either by direct contact with animals or food products or indirectly via environmental pathways and/or non-food producing animals Figure 1 17. Wildlife is a major zoonotic origin of transmission of various bacterial genes and hence the diseases among the domestic animals and human ecosystem 18. Global distribution of E. coli harboring MCR-1 gene Wild birds and animals are the potential reservoirs and vectors for the global distribution of MCR-1 it has been identifed on Enterobacteriaceae isolates from food-producing animals companion animal food products the environment and humans worldwide 219. Te gene has been found primarily in E. coli but has also been identifed in other members of the Enterobacteriaceae in human animal food and environmental samples on every continent 20. Te MCR-1 gene has been rapidly detected in several European Asian South-East Asian South American Northern American and African countries. Retrospective studies led to establishing the presence of the MCR-1 gene in China as early as the 1980s and in Europe since 2005 21. Te global distribution of MCR-1 over at least fve continents is well documented but little is known about its origin acquisition emergence and spread 22. A plasmid-mediated horizontally transferable colistin resistance MCR-1 gene was recently reported in China and subsequently detected in Asia Vietnam Laos Tailand Cambodia Malaysia Singapore Taiwan and Japan Europe Te Netherlands Germany Belgium Switzerland France Denmark United Kingdom Spain Italy Sweden and Portugal Africa Algeria Egypt South Africa and Tunisia and America Canada Argentina and Brazil 23. Continental plasmid profle and phenotypic characteristics of E. coli harbouring MCR-1 gene of wildlife origin A brief summary is given below in Table 1 Continents in which the MCR-1 harboring colistin resistance gene has been reported from E. coli of only wildlife origin so far: Te frst report of the dissemination of the MCR-1 gene in Kelp gulls is from ushuaia Argentina. Te fact that gull species migrate sometimes even between continents indicates that they may play a role in the global dissemination of these clinically relevant bacteria. Te association of the MCR-1 gene with conjugative IncI2 plasmids also among gulls illustrates a successful plasmid–gene combination resulting in the emergence spread of this gene 24. Te frst known occurrence of the MCR-1 gene in E. coli carried by a wild migratory bird- the European herring gull Larus argentatus 25. Te frst detection of MCR-1 in colistin-resistant extended spectrum β-lactamase-producing E. coli ESBL-E. coli isolated from wild transboundary migratory waterfowl species Fulica atra from Pakistan Asia26. Conclusion No doubts a set of data has been reported so far from wildlife 24-26.But it is not sufcient to estimate and account for MCR-1 gene distribution in E. coli wildlife globally. Tere is an urgent need and we emphasize to look for MCR-1 gene not only in birds but also in animals. Although birds can travel and disseminate more than animals but we cannot neglect the impact of interaction between domestic and wildlife animals as indicated from wild animals in Poland 16. Also we suggest investigating MCR-1 gene presence in other continents of Figure 1: Interactions between groups. Antimicrobial‐resistant bacteria can spread to humans either by the food supply direct contact with food or companion animals or more indirectly through environmental pathways including waterways soils and vegetables contaminated with human or animals waste and vectors such as rodents insects and birds 17. Continents Country Species ST-type Plasmid Year 1 - South America Argentina Larus dominicanus 1. ST101 2. ST744 IncI2 2016 2- Europe Lithuania Larus argentatus - SHP45 2016 3- Asia Pakistan Fulica atra ST354 IncI2 2016 Table: 1 MCR-1 in wildlife of Subcontinents.

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Citation: Shad AA 2019 MCR-1 Colistin Resistance in Escherichia coli Wildlife: A Continental Mini-reviewy. J Drug Metab Toxicol 9: 243. doi:10.4172/2157-7609.1000243 Page 3 of 3 Volume 9 • Issue 3 • 1000243 J Drug Metab Toxicol an open access journal ISSN: 2157-7609 wildlife so that a more comprehensive picture can be established in accounting MCR-1 gene. References 1. Liu YY Wang Y Walsh TR Yi LX Zhang R et al. 2015 Emergence of plasmid- mediated colistin resistance mechanism MCR-1 in animals and human beings in China: a microbiological and molecular biological study. Lancet Infect Dis 16: 161-168. 2. Wang J Ma ZB Zeng ZL Yang XW Huang Y et al. 2017 The role of wildlife wild birds in the global transmission of antimicrobial resistance genes. Zool Res 38: 55-80. 3. Castanheira M Griffn MA Deshpande LM Mendes RE Jones RN et al. 2016 Detection of mcr-1 among Escherichia coli clinical isolates collected worldwide as part of the SENTRY Antimicrobial Surveillance Program. Antimicrob Agents Chemother 60: 5623-5624. 4. Skov RL Monnet DL 2016 Plasmid-mediated colistin resistance mcr-1 gene: three months later the story unfolds. Euro Surveill 21: 30155. 5. Schwarz S Johnson AP 2016 Transferable resistance to colistin: a new but old threat. J Antimicrob Chemother 71: 2066-2070. 6. Taj MK Zohra S Ji Xiu Imran 2014 Escherichia coli as a model organism. Int J Engg Res Sci Tech 3: 1-8. 7. Wirth T Falush D Lan R Colles F Mensa P et al. 2006 Sex and virulence in Escherichia coli: an evolutionary Perspective. Mol Microbiol 60: 1136-1151. 8. Jafari A Aslani MM Bouzari S 2012 Escherichia coli: a brief review of diarrheagenic pathotypes and their role in diarrheal diseases in Iran. Iran J Microbiol 4: 102. 9. Tahir H 2015 An introduction to the serotypes pathotypes and phylotypes of Escherichia coli” Int J Microbiol Allied Sci 2: 9-16. 10. Guixing Ma Zhu Y Yu Z Ahmad A Zhang H 2016 High resolution crystal structure of the catalytic domain of MCR1. Scientifc Reports 6: 39540. 11. Sun J Zhang H Liu YH Feng Y 2018 Towards understanding MCR-like colistin resistance. Trends Microbiol 26.9:794-808. 12. Chen K Chan EW Xie M Ye L Dong N et al. 2017 Widespread distribution of mcr-1-bearing bacteria in the Ecosystem. Euro Surveill 22: 39 13. Zhang J Chen L Wang J Butaye P Huang K et al. 2018 Molecular detection of colistin resistance genes mcr-1 to mcr-5 in human vaginal swabs. BMC Research Notes 11: 143. 14. Yanat B Machuca J Yahia RD Touati A Rodriguez M et al. 2016 First report of the plasmid-mediated colistin resistance gene mcr-1 in a clinical Escherichia coli isolate in Algeria. Int J Antimicrob Agents 48.6:760. 15. Laurent P Patrice N 2016 Emerging plasmid-encoded colistin resistance: the animal world as the culprit J Antimicrob Chemother 71: 2326–2327. 16. Wasyl D Magdalena Z Anna L Magdalena S 2017 Antimicrobial resistance in Escherichia coli isolated from wild animals in Poland. Microbial Drug Resistanc 24: 0184. 17. Argudín MA Deplano A Meghraoui A Dodemont M Heinrichs A et al. 2017 Bacteria from animals as a pool of antimicrobial resistance genes. Antibiotics 6: 12. 18. Kruse H Anne MK Kjell H 2004 Wildlife as source of zoonotic infections. Emerg infect dis 10: 2067. 19. Huang X Linfeng YU Xiaojie C Chanping Z XU Y et al.2017 High prevalence of colistin resistance and mcr-1 gene in Escherichia coli isolated from food animals in China. Front Microbiol 8: 562. 20. McGann P Snesrud E Maybank R Corey B Ong AC et al. 2016 Escherichia coli harboring mcr-1 and blaCTX-M on a novel IncF plasmid: frst report of mcr- 1 in the United States. Antimicrob Agents Chemother 60: 4420-4421. 21. Lepelletier D.2018. “Emergence of plasmid-mediated colistin resistance mcr- 1 among Enterobacteriaceae strains: Laboratory detection of resistance and measures to control its dissemination.” Medecine maladies infectieuses 48.4: 250-255 22. Wang R Lucy V Liam P Phelim B Qi Wet al. 2018 The global distribution and spread of the mobilized colistin resistance gene mcr-1. Nature communications 9: 1179 23. Kwang P Jung HL Moonhee P Kwan SK Sang HL 2017 How many mcr-1- harbouring bacteria were spreading geographically. Biomedical Research 28. 24. Liakopoulos A Dik JM Bjorn O Jonas b 2016 The colistin resistance mcr- 1 gene is going wild.” Journal of Antimicrobial Chemotherapy 71: 2335-2336 25. Ruzauskas M Lina V 2016 Detection of the mcr-1 gene in Escherichia coli prevalent in the migratory bird species Larus argentatus. J Antimicrob Chemother 71: 2333-2334. 26. Mohsin M Raza S Roschanski N Schaulfer K Guenther S.2016 “First description of plasmid-mediated colistin-resistant extended-spectrum β-lactamase-producing Escherichia coli in a wild migratory bird from Asia. Int J Antimicrob Agents 48: 463-464.

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