A One-Health Sampling Strategy to Explore the Dissemination and Relationship Between Colistin Resistance in Human, Animal, and Environmental Sectors in Laos
Yuqing Zhou,
Refath Farzana,
Somsavanh Sihalath,
Sayaphet Rattanavong,
Manivanh Vongsouvath,
Mayfong Mayxay,
Kirsty Sands,
Paul N. Newton,
David A.B. Dance,
Brekhna Hassan,
Timothy R. Walsh
Affiliations
Yuqing Zhou
Department of Zoology, University of Oxford, Oxford OX1 3SZ, UK; Ineos Oxford Institute for Antimicrobial Research (IOI), University of Oxford, Oxford OX1 3RE, UK; Department of Medical Microbiology, Institute of Infection and Immunity, School of Medicine, Cardiff University, Cardiff CF14 4XN, UK; Corresponding author.
Refath Farzana
Department of Zoology, University of Oxford, Oxford OX1 3SZ, UK; Ineos Oxford Institute for Antimicrobial Research (IOI), University of Oxford, Oxford OX1 3RE, UK; Department of Medical Microbiology, Institute of Infection and Immunity, School of Medicine, Cardiff University, Cardiff CF14 4XN, UK
Somsavanh Sihalath
Lao-Oxford-Mahosot Hospital-Wellcome Trust Research Unit, Microbiology Laboratory, Mahosot Hospital, Vientiane PO Box 292, Lao PDR
Sayaphet Rattanavong
Lao-Oxford-Mahosot Hospital-Wellcome Trust Research Unit, Microbiology Laboratory, Mahosot Hospital, Vientiane PO Box 292, Lao PDR
Manivanh Vongsouvath
Lao-Oxford-Mahosot Hospital-Wellcome Trust Research Unit, Microbiology Laboratory, Mahosot Hospital, Vientiane PO Box 292, Lao PDR
Mayfong Mayxay
Lao-Oxford-Mahosot Hospital-Wellcome Trust Research Unit, Microbiology Laboratory, Mahosot Hospital, Vientiane PO Box 292, Lao PDR; Centre for Tropical Medicine & Global Health, Nuffield Department of Medicine, University of Oxford, Oxford OX3 7BN, UK; Institute of Research and Education Development, University of Health Sciences, Vientiane PO Box 7444, Lao PDR
Kirsty Sands
Department of Zoology, University of Oxford, Oxford OX1 3SZ, UK; Ineos Oxford Institute for Antimicrobial Research (IOI), University of Oxford, Oxford OX1 3RE, UK; Department of Medical Microbiology, Institute of Infection and Immunity, School of Medicine, Cardiff University, Cardiff CF14 4XN, UK
Paul N. Newton
Lao-Oxford-Mahosot Hospital-Wellcome Trust Research Unit, Microbiology Laboratory, Mahosot Hospital, Vientiane PO Box 292, Lao PDR; Centre for Tropical Medicine & Global Health, Nuffield Department of Medicine, University of Oxford, Oxford OX3 7BN, UK; Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London WC1E 7HT, UK
David A.B. Dance
Lao-Oxford-Mahosot Hospital-Wellcome Trust Research Unit, Microbiology Laboratory, Mahosot Hospital, Vientiane PO Box 292, Lao PDR; Centre for Tropical Medicine & Global Health, Nuffield Department of Medicine, University of Oxford, Oxford OX3 7BN, UK; Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London WC1E 7HT, UK
Brekhna Hassan
Department of Medical Microbiology, Institute of Infection and Immunity, School of Medicine, Cardiff University, Cardiff CF14 4XN, UK
Timothy R. Walsh
Department of Zoology, University of Oxford, Oxford OX1 3SZ, UK; Ineos Oxford Institute for Antimicrobial Research (IOI), University of Oxford, Oxford OX1 3RE, UK
This study was designed to investigate the molecular epidemiology of mobile colistin resistance (mcr) using a “One-Health” approach in Laos and to predict whether any dominant plasmid backbone and/or strain type influences the dissemination of mcr. We collected 673 samples from humans (rectal normal flora), poultry, and the environment (water, flies, birds, etc.) in Vientiane, Lao People’s Democratic Republic (Laos), from May to September 2018. A total of 238 Escherichia coli (E. coli) isolated from non-duplicative samples, consisting of 98 MCR-positive E. coli (MCRPEC) (“mcr” denotes the gene encoding mobile colistin resistance, and “MCR” denotes the subsequent protein encoded by mcr) and 140 MCR-negative E. coli (MCRNEC), were characterized by phenotype and Illumina sequencing. A subset of MCRPEC was selected for MinION sequencing, conjugation assay, plasmid stability, and growth kinetics in vitro. The prevalence of MCRPEC was found to be 14.6% (98/673), with the highest prevalence in human rectal swabs (45.9% (45/98), p < 0.0001, odds ratio (OR): 0.125, 95% confidence interval (CI): 0.077–0.202). The percentages of MCRPEC from other samples were 14.3% (2/14) in dog feces, 12.0% (24/200) in flies, 11.0% (11/100) in chicken meat, 8.9% (8/90) in chicken cloacal, 8.0% (4/50) in chicken caeca, and 7.5% (4/53) in wastewater. MCRPEC was significantly more resistant to co-amoxiclav, sulfamethoxazole-trimethoprim, levofloxacin, ciprofloxacin, and gentamicin than MCRNEC (p < 0.05). Genomic analysis revealed the distribution of MCRPEC among diverse clonal types. The putative plasmid Inc types associated with mcr-1 were IncX4, IncHI2, IncP1, IncI2, and IncFIA, and those associated with mcr-3 were IncFII, IncFIA, IncFIB, IncP1, and IncR. Recovery of highly similar plasmids from both flies and other sampling sectors implied the role of flies in the dissemination of mcr-1. mcr-positive plasmids were shown to be conjugative, and a significantly high transfer rate into a hypervirulent clone ST1193 was observed. Plasmids containing mcr irrespective of Inc type were highly stable and invariably did not exert a fitness effect upon introduction into a new host. These findings signify the urgent need for a standard infection control program to radically decontaminate the source of resistance.
