Emergence of plasmid-mediated fosfomycin resistance among Escherichia coli harboring fosA4, tet(X4), and mcr-1 genes in wild birds

ABSTRACT Fosfomycin represents a last-line reserve antibiotic for the treatment of infections caused by multidrug-resistant (MDR) bacteria. Nevertheless, the advent of plasmid-mediated fosfomycin resistance among bacteria from humans and food animals incurs great concern. This study reports the dete...

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Main Authors: Asim Munir, Xiaoyu Lu, Farwa Humak, Cemil Kürekci, Muhammad Shahid Mahmood, Sehrish Gul, Zhiqiang Wang, Mashkoor Mohsin, Ruichao Li
Format: Article
Language:English
Published: American Society for Microbiology 2025-04-01
Series:mSystems
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Online Access:https://journals.asm.org/doi/10.1128/msystems.01673-24
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author Asim Munir
Xiaoyu Lu
Farwa Humak
Cemil Kürekci
Muhammad Shahid Mahmood
Sehrish Gul
Zhiqiang Wang
Mashkoor Mohsin
Ruichao Li
author_facet Asim Munir
Xiaoyu Lu
Farwa Humak
Cemil Kürekci
Muhammad Shahid Mahmood
Sehrish Gul
Zhiqiang Wang
Mashkoor Mohsin
Ruichao Li
author_sort Asim Munir
collection DOAJ
description ABSTRACT Fosfomycin represents a last-line reserve antibiotic for the treatment of infections caused by multidrug-resistant (MDR) bacteria. Nevertheless, the advent of plasmid-mediated fosfomycin resistance among bacteria from humans and food animals incurs great concern. This study reports the detection and genomic portrait of the plasmid-mediated fosfomycin resistance gene, fosA4, amid Escherichia coli from wild birds co-harboring plasmid-mediated tigecycline resistance gene, tet(X4), and colistin resistance gene, mcr-1. A total of 100 samples from fecal droppings of wild birds in the urban parks in Faisalabad, Pakistan were subjected for the isolation and characterization of fosfomycin-resistant E. coli. The fosA4 gene was identified in 11 (11%) of the E. coli isolates, and all exhibited an MDR phenotype. Genome sequencing confirmed that all the fosA4-positive isolates also co-harbored the mobile tigecycline resistance tet(X4) gene on a large MDR IncFII plasmid. One isolate PKF8 belonging to ST48 also co-carried the colistin resistance gene mcr-1 on the IncHI2 plasmid. To the extent of our knowledge, this is the first discovery of E. coli isolates in wild birds co-harboring the mcr-1, fosA4, and tet(X4) genes. The emergence of these pivotal antimicrobial resistance genes in wild birds native to South Asia with their close association to humans and animals is alarming. Our findings highlight the urgent need for further surveillance of bacterial resistance to last-resort antibiotics in the clinics, animal farming, and environment with the One Health approach.IMPORTANCEThe global spread of the plasmid-mediated fosfomycin resistance gene fosA4 bearing Escherichia coli strains incurs a public health concern. However, research focusing on the pervasiveness of fosA4-positive isolates in wild birds is still rare, and to the best of our knowledge, this is the first documentation from South Asia highlighting the concurrent presence of the fosA4, mcr-1, and tet(X4) genes within E. coli isolates recovered from fecal samples of wild birds in Pakistan. This co-existence of ARGs along with phylogenetic analysis revealed that MDR plasmids carried by E. coli isolates have the ability to spread horizontally between wild birds, food animals, and humans. Co-existence of fosA4, tet(X4), and mcr-1-carrying plasmids is worrying and warrants further investigation.
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spelling doaj-art-a2333a28b3334ad6b53f2bc5dd60e6f32025-08-20T03:13:21ZengAmerican Society for MicrobiologymSystems2379-50772025-04-0110410.1128/msystems.01673-24Emergence of plasmid-mediated fosfomycin resistance among Escherichia coli harboring fosA4, tet(X4), and mcr-1 genes in wild birdsAsim Munir0Xiaoyu Lu1Farwa Humak2Cemil Kürekci3Muhammad Shahid Mahmood4Sehrish Gul5Zhiqiang Wang6Mashkoor Mohsin7Ruichao Li8Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, College of Veterinary Medicine, Yangzhou University, Yangzhou, ChinaJiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, College of Veterinary Medicine, Yangzhou University, Yangzhou, ChinaInstitute of Microbiology, University of Agriculture, Faisalabad, PakistanDepartment of Food Hygiene and Technology, Faculty of Veterinary Medicine, Hatay Mustafa Kemal University, Hatay, TurkeyInstitute of Microbiology, University of Agriculture, Faisalabad, PakistanInstitute of Microbiology, University of Agriculture, Faisalabad, PakistanJiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, College of Veterinary Medicine, Yangzhou University, Yangzhou, ChinaInstitute of Microbiology, University of Agriculture, Faisalabad, PakistanJiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, College of Veterinary Medicine, Yangzhou University, Yangzhou, ChinaABSTRACT Fosfomycin represents a last-line reserve antibiotic for the treatment of infections caused by multidrug-resistant (MDR) bacteria. Nevertheless, the advent of plasmid-mediated fosfomycin resistance among bacteria from humans and food animals incurs great concern. This study reports the detection and genomic portrait of the plasmid-mediated fosfomycin resistance gene, fosA4, amid Escherichia coli from wild birds co-harboring plasmid-mediated tigecycline resistance gene, tet(X4), and colistin resistance gene, mcr-1. A total of 100 samples from fecal droppings of wild birds in the urban parks in Faisalabad, Pakistan were subjected for the isolation and characterization of fosfomycin-resistant E. coli. The fosA4 gene was identified in 11 (11%) of the E. coli isolates, and all exhibited an MDR phenotype. Genome sequencing confirmed that all the fosA4-positive isolates also co-harbored the mobile tigecycline resistance tet(X4) gene on a large MDR IncFII plasmid. One isolate PKF8 belonging to ST48 also co-carried the colistin resistance gene mcr-1 on the IncHI2 plasmid. To the extent of our knowledge, this is the first discovery of E. coli isolates in wild birds co-harboring the mcr-1, fosA4, and tet(X4) genes. The emergence of these pivotal antimicrobial resistance genes in wild birds native to South Asia with their close association to humans and animals is alarming. Our findings highlight the urgent need for further surveillance of bacterial resistance to last-resort antibiotics in the clinics, animal farming, and environment with the One Health approach.IMPORTANCEThe global spread of the plasmid-mediated fosfomycin resistance gene fosA4 bearing Escherichia coli strains incurs a public health concern. However, research focusing on the pervasiveness of fosA4-positive isolates in wild birds is still rare, and to the best of our knowledge, this is the first documentation from South Asia highlighting the concurrent presence of the fosA4, mcr-1, and tet(X4) genes within E. coli isolates recovered from fecal samples of wild birds in Pakistan. This co-existence of ARGs along with phylogenetic analysis revealed that MDR plasmids carried by E. coli isolates have the ability to spread horizontally between wild birds, food animals, and humans. Co-existence of fosA4, tet(X4), and mcr-1-carrying plasmids is worrying and warrants further investigation.https://journals.asm.org/doi/10.1128/msystems.01673-24antimicrobial resistancewild birdsE. colifosA4mcr-1tet(X4)
spellingShingle Asim Munir
Xiaoyu Lu
Farwa Humak
Cemil Kürekci
Muhammad Shahid Mahmood
Sehrish Gul
Zhiqiang Wang
Mashkoor Mohsin
Ruichao Li
Emergence of plasmid-mediated fosfomycin resistance among Escherichia coli harboring fosA4, tet(X4), and mcr-1 genes in wild birds
mSystems
antimicrobial resistance
wild birds
E. coli
fosA4
mcr-1
tet(X4)
title Emergence of plasmid-mediated fosfomycin resistance among Escherichia coli harboring fosA4, tet(X4), and mcr-1 genes in wild birds
title_full Emergence of plasmid-mediated fosfomycin resistance among Escherichia coli harboring fosA4, tet(X4), and mcr-1 genes in wild birds
title_fullStr Emergence of plasmid-mediated fosfomycin resistance among Escherichia coli harboring fosA4, tet(X4), and mcr-1 genes in wild birds
title_full_unstemmed Emergence of plasmid-mediated fosfomycin resistance among Escherichia coli harboring fosA4, tet(X4), and mcr-1 genes in wild birds
title_short Emergence of plasmid-mediated fosfomycin resistance among Escherichia coli harboring fosA4, tet(X4), and mcr-1 genes in wild birds
title_sort emergence of plasmid mediated fosfomycin resistance among escherichia coli harboring fosa4 tet x4 and mcr 1 genes in wild birds
topic antimicrobial resistance
wild birds
E. coli
fosA4
mcr-1
tet(X4)
url https://journals.asm.org/doi/10.1128/msystems.01673-24
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