Recent data re-affirm antimicrobial resistance (AMR) as a One Health problem, particularly in low- and middle-income countries. Transdisciplinary and intersectoral collaboration are required

if we are to improve environmental hygiene, addressing both AMR and a range of aligned development challenges. Antimicrobial resistance (AMR) has been described as “the quintessential One

Health problem” and it is believed that any meaningful effort to ameliorate this global public health challenge will require transdisciplinary and intersectoral collaboration to improve

health for humans, animals and the environment1. There is not, however, enough evidence describing how antimicrobial resistant bacteria flow between different ecological compartments, or

interventions to control AMR, especially as strong, potentially competing cases can be made to focus resources on antimicrobial stewardship and/or infection, prevention and control (IPC)

practices in health care facilities on one hand, and water, sanitation and hygiene (WASH) practices in community settings on the other hand. Filling this evidence gap has become more

pressing given that several recent studies, mostly from high-income settings, have shown limited evidence of a role for animal and environmental reservoirs in the human acquisition of key

AMR pathogens. LIMITED EVIDENCE FOR AMR AS A ONE HEALTH PROBLEM IN HIGH-INCOME COUNTRIES A study of extended spectrum beta-lactamase (ESBL) producing _E. coli_ by Public Health England (now

UK Health Security Agency) compared isolates from human faeces, sewage, farm slurry, and retail foodstuffs to human bloodstream infection (BSI) isolates and found little overlap between

non-human reservoirs and isolates from invasive human disease2. Similarly, a genomic surveillance of _E. coli_ in the UK found distinct lineages and mobile genetic elements of _E. coli_

between human BSI and livestock samples3. A recent study of _Klebsiella pneumoniae_ from a wide range of clinical, community, animal and environmental settings in Italy, described by the

authors as “a hotspot for hospital-acquired carbapenem non-susceptible _Klebsiella_”, found no genotypic or phenotypic evidence for non-susceptibility to carbapenems outside the clinical

environment4. In these studies, a lack of relatedness between bacterial isolates found in human infection samples and isolates from other ecological sources may not equate to a lack of

transmission between ecological compartments. The sampling strategies employed including sampling animals from closed farms alongside unlinked humans from a large geographical area, may have

influenced the ability to detect significant or potential transmission events5. EMERGING DATA RE-AFFIRM AMR IS A ONE HEALTH PROBLEM IN LMICS On the other hand, some studies have shown

evidence for a strong association between poor environmental health infrastructure and AMR, particularly affecting the most vulnerable populations in the world6. The Drivers of Resistance in

Uganda and Malawi (DRUM) study, collected demographic, geospatial, clinical, animal husbandry and environmental health (including WASH infrastructure and practice) data from households in

urban, peri-urban and rural settings in Uganda and Malawi7. Longitudinal human, animal and environmental sampling at each household was used to isolate ESBL _E. coli_ and ESBL _K.

pneumoniae_. Multivariable models illustrated that human ESBL-producing _E. coli_ colonisation was associated with the wet season and close animal interaction, and that without adequate

efforts to improve environmental health, ESBL-producing Enterobacteriaceae transmission is likely to persist in these settings8,9. _E. coli_ is a highly diverse species, and the resolution

offered by whole genome sequencing (WGS) reveals that sub-groups of _E. coli_, even at the level of discrimination offered by multi-locus sequence typing are generally distinct in different

ecological sources. Despite this, there is flow of antimicrobial resistant strains or AMR genes between one health compartments. This is particularly evident in sub-Saharan Africa (sSA),

where analysis of _E. coli_ genomes from the UrbanZoo study in Kenya demonstrated that although transmission of the general _E. coli_ population is often within host species10, there is

significant flux of accessory genes on mobile genetic elements (MGE), especially AMR genes, between humans and animals11,12. Sharing of the accessory genomes across different sources was

also observed among _K. pneumoniae_ isolates from clinical, environmental, and animal sources in Ghana, an indication of transmission of _K. pneumoniae_ between the different compartments13.

In Malawi and Uganda, comparison of _E. coli_ genomes revealed high diversity of _E. coli_, MGE and ESBL genes that were distributed independent of ecological compartments14. Detailed

lineage level SNP analysis of these genomes further indicated putative transmission events of ESBL-_E. coli_ between humans, animals and the environment14. Outside sSA and Europe, evidence

of phylogenetic intermixing and sharing of AMR genes between humans, animals and soil has been reported in Bangladesh15. Similarly, in Ecuador, significant clonal and AMR gene sharing of

third generation cephalosporin resistant _E. coli_ was observed between children and animals, suggesting interlinkage of AMR in animals and humans16. The degree of sharing of bacteria

strains and AMR determinants between different ecological compartments reported in studies such as these is certainly underestimated. This is particularly the case because carriage studies

involving isolate WGS do not fully account for within sample diversity. Nevertheless, even without capturing that full diversity, the available evidence suggests exchange of AMR bacterial

strains and AMR determinants between the different ecological compartments is common, particularly in low- and middle-income countries (LMICs). WASH SYSTEMS AND THE SPREAD OF AMR ACROSS

ECOLOGICAL COMPARTMENTS Detection of closely related ESBL-producing Enterobacteriaceae in humans, animals and the environment within LMICs not only illustrates the relevance of the One

Health paradigm to key AMR human pathogens, but is also a manifestation of the poor environmental health standards and practices combined with the close interactions between humans, animals

and the environment. Although not a surprise to the WASH community, the prominence of AMR as a global health issue can be used to shine new light on the urgency to address Sustainable

Development Goal 6: ensuring the universal and equitable access to WASH for all. This could be effectively utilised to catalyse renewed enthusiasm and commitment for investment in WASH

infrastructure, with aligned effective social and behaviour change programmes to reduce the interactions between these different ecological sources. On the other hand, the fact there is

limited evidence for ESBL-_E. coli_ and _K. pneumoniae_ transmission between humans, animals and the environment in settings such as Europe where WASH infrastructure is strong, highlights

the central role context appropriate approaches to improving environmental hygiene must play. The presence of these bacteria in healthcare settings informs us that IPC strategy in these

settings is failing, placing patients at risk of adverse outcomes. Indeed, a high prevalence of healthcare associated infection, in part, illustrates a failure of environmental hygiene

measures and practices in healthcare settings17. The response to AMR must not only be contextually appropriate, but also take a whole system approach, understanding that infection prevention

is broader than the practice of IPC in healthcare facilities, and should embrace WASH infrastructure and practice in domestic, public and institutional settings. Indeed, to prevent severe

bacterial infection from ESBL-_E. coli_, asymptomatic transmission of ESBL-enteric bacteria needs to be interrupted. AMR does not recognise the disciplinary silos in which we typically

operate and the presence of widespread ESBL-enteric bacteria indicates that we are failing to create effective, equitable and sustainable access to basic WASH infrastructure and services for

the most vulnerable populations in the world. CONCLUSION Evidence for a One Health Framework for AMR remains incomplete. While some studies have provided evidence of the need to take a One

Health approach to AMR, such approaches will differ according to setting. Acknowledging however, that environments in LMIC are commonly contaminated by AMR bacteria such as ESBL–producing

_E. coli_ and _K. pneumoniae_ and therefore unsafe, is a critical starting point. It demonstrates the need for a whole system approach to environmental hygiene, in which we will see

catalytic and reinforcing advantages from transdisciplinary working to develop context appropriate and sustainable solutions that tackle global public health, economic development, dignity

and wellbeing simultaneously by improving WASH infrastructure and practice. Bacterial populations must be segregated by introducing transmission bottlenecks between human, animal and

environmental compartments to reduce overall AMR transmission rates. To achieve this, there is an urgent need for designing, validating and understanding how best to implement such

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AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * Malawi Liverpool Wellcome Programme, Blantyre, Malawi Patrick Musicha, Derek Cocker & Nicholas A. Feasey * Liverpool School of Tropical

Medicine, Liverpool, UK Patrick Musicha & Nicholas A. Feasey * University of Strathclyde, Glasgow, UK Tracy Morse * University of Liverpool, Liverpool, UK Derek Cocker * Makerere

University, College of Veterinary Medicine, Animal Resources and Biosecurity, Kampala, Uganda Lawrence Mugisha * Lancaster University, Lancaster, UK Christopher P. Jewell * University of St.

Andrews, St. Andrews, UK Nicholas A. Feasey Authors * Patrick Musicha View author publications You can also search for this author inPubMed Google Scholar * Tracy Morse View author

publications You can also search for this author inPubMed Google Scholar * Derek Cocker View author publications You can also search for this author inPubMed Google Scholar * Lawrence

Mugisha View author publications You can also search for this author inPubMed Google Scholar * Christopher P. Jewell View author publications You can also search for this author inPubMed 

Google Scholar * Nicholas A. Feasey View author publications You can also search for this author inPubMed Google Scholar CONTRIBUTIONS P.M. and N.A.F. conceived this work. P.M., T.M.,

C.P.J., and N.A.F. wrote the manuscript, with critical revision by D.C. and L.M. All the authors read and approved the final version of the manuscript. CORRESPONDING AUTHOR Correspondence to

Patrick Musicha. ETHICS DECLARATIONS COMPETING INTERESTS The authors declare no competing interests. PEER REVIEW PEER REVIEW INFORMATION _Nature Communications_ thanks the anonymous

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ARTICLE Musicha, P., Morse, T., Cocker, D. _et al._ Time to define One Health approaches to tackling antimicrobial resistance. _Nat Commun_ 15, 8782 (2024).

https://doi.org/10.1038/s41467-024-53057-z Download citation * Received: 16 November 2023 * Accepted: 26 September 2024 * Published: 10 October 2024 * DOI:

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