This month, a high-level meeting on antimicrobial resistance (AMR) organized by The UN General Assembly will take place on the 26th of September in New York, USA ⁽¹⁾. Global leaders will come together and agree on actions needed to tackle the threat of AMR.

AMR is the ability of a pathogen to survive exposure to antimicrobial agents that previously were an effective treatment. Such pathogens usually acquire AMR through mutations in specific genes or through gene transfer; when a microorganism acquires multiple genetic changes making it resistant to multiple antimicrobials, this pathogen is then called a multi-drug resistant organisms (MDRO), more commonly known as a “superbug”. It has been estimated that 4.95 million deaths were associated with AMR in 2019 ⁽²⁾, with this number predicted to increase to 10 million per year by 2050 ⁽³⁾. As we all know too well, pathogens do not recognize borders and can spread between environments, which means that they are everyone’s problem, and global equitable solutions need to be sought out.

Whole genome sequencing (WGS) allows us to look at the full genetic makeup of the pathogen such as genetic features that allow us to characterize them based on genotype, virulence genes and genomic changes or acquired genes conferring resistance to antibiotics; as well as providing insights into evolutionary changes in pathogen populations when investigating genomes from longitudinal studies. Overall, genomics has great potential to assist outbreak investigation, pathogen surveillance and help to detect difficult to grow pathogens, identify novel types of pathogens and novel antimicrobial resistance determinants.

Genomics so far has been instrumental in helping to track pathogenicity of particular clinically-relevant pathogens ⁽⁴⁾, detect outbreaks and the source of the outbreak ^(5,6), track novel and emerging AMR trends ^(7,8) and understand better how AMR can spread through horizontal gene transfer in hospital settings ^(9,10). Additionally, genomics has put a higher importance on looking into AMR emergence and spread with ‘ONE Health’ view, with studies reporting on zoonotic exchange of bacterial pathogens and AMR genes between the environment, animals, and humans ^(11-13), understanding the drivers for exchange of AMR between different interfaces will allow to make informed actions for intervention.

How can we better utilise genomics and implement it as integral part of our fight against AMR?

A SECRIC Working Group on Genomics for AMR Surveillance (https://sedric.org.uk/working- groups/) has published 9 recommendations ⁽¹⁴⁾ on what needs to happen to help implement genomics into AMR surveillance whilst discussing current advantages and challenges faced for implementing genomics for AMR Surveillance in health laboratories, public health networks and One Health ^(15-19). WHO GLASS (Global Antimicrobial Resistance Surveillance system) has also published overview of benefits and limitations of implementing current WGS technologies into routine surveillance ⁽²⁰⁾. A number of very successful workshops aimed at building capacity for bioinformatics and genomic sequencing for AMR surveillance workshops aimed at building capacity has taken place and were funded by Wellcome Trust ⁽²¹⁾ and Fleming Fund ⁽²²⁾.

What can we do to help fight AMR?

You can help by getting involved and organising activities to engage your family, institution, public, policy members, and colleagues in learning more about AMR during World Antimicrobial Awareness Week (WAAW), which will take place from November 18 to 24, 2024.

References:

1. The UN Meeting on AMR: https://www.who.int/news-room/events/detail/2024/09/26/default- calendar/un-general-assembly-high-level-meeting-on-antimicrobial-resistance-2024
2. Murray et al, 2022: Global burden of bacterial antimicrobial resistance in 2019: a systematic analysis; doi: https://doi.org/10.1016/S0140-6736(21)02724-0
3. O’Neil report May 2016: doi: https://amr- review.org/sites/default/files/160525_Final%20paper_with%20cover.pdf
4. Heinz E, et al 2024: Longitudinal analysis within one hospital in sub-Saharan Africa over 20 years reveals repeated replacements of dominant clones of Klebsiella pneumoniae and stresses the importance to include temporal patterns for vaccine design considerations, doi: https://doi.org/10.1186/s13073-024-01342-3
5. Self JL et al, 2019: Multistate Outbreak of Listeriosis Associated with Packaged Leafy Green Salads, United States and Canada, 2015-2016, doi: https://doi.org/10.3201%2Feid2508.180761
6. Bottichio L, et al, 2020: Shiga Toxin-Producing Escherichia coli Infections Associated With Romaine Lettuce-United States, 2018, doi: https://doi.org/10.1093/cid/ciz1182
7. Alba P, et al, 2018: Molecular Epidemiology of mcr-Encoded Colistin Resistance in Enterobacteriaceae From Food-Producing Animals in Italy Revealed Through the EU
Harmonized Antimicrobial Resistance Monitoring, doi: https://doi.org/10.3389/fmicb.2018.01217
8. Forde BM, Zowawi HM, et al, 2018: Discovery of mcr-1-Mediated Colistin Resistance in a Highly Virulent Escherichia coli Lineage, doi: https://doi.org/10.1128%2FmSphere.00486-18
9. Evans DR, et al, 2020: Systematic detection of horizontal gene transfer across genera among multidrug-resistant bacteria in a single hospital, doi: https://doi.org/10.7554/eLife.53886
10. Wan Y, Myall AC, Boonyasiri A, 2024: Integrated Analysis of Patient Networks and Plasmid Genomes to Investigate a Regional, Multispecies Outbreak of Carbapenemase-Producing Enterobacterales Carrying Both blaIMP and mcr-9 Genes, doi: https://doi.org/10.1093/infdis/jiae019
11. Mwapasa T., et al, 2024: Key environmental exposure pathways to antimicrobial resistant bacteria in southern Malawi: A SaniPath approach, doi: https://doi.org/10.1016/j.scitotenv.2024.174142
12. Cocker D., et al 2023: Investigating One Health risks for human colonisation with extended spectrum β-lactamase-producing Escherichia coli and Klebsiella pneumoniae in Malawian households: a longitudinal cohort study, doi: https://doi.org/10.1016/s2666-5247(23)00062-9
13. Mourkas E., et al, 2024: Proximity to humans is associated with antimicrobial-resistant enteric pathogens in wild bird microbiomes, doi: https://doi.org/10.1016/j.cub.2024.07.059
14. Harnessing genomics for AMR surveillance Policy Brief: https://sedric.org.uk/wp- content/uploads/2022/06/SEDRIC_infographic_23-06-2022.pdf
15. Baker KS, Jauneikaite E., et al, 2023: Evidence review and recommendations for the implementation of genomics for antimicrobial resistance surveillance: reports from an international expert group; doi: https://doi.org/10.1016/s2666-5247(23)00281-1
16. Jauneikaite E. et al, 2023: Genomics for antimicrobial resistance surveillance to support infection prevention and control in health-care facilities, doi: https://doi.org/10.1016/s2666-5247(23)00282-3
17. Baker KS, et al, 2023: Genomics for public health and international surveillance of antimicrobial resistance, doi: https://doi.org/10.1016/s2666-5247(23)00283-5
18. Muloi DM, et al, 2023: Exploiting genomics for antimicrobial resistance surveillance at One Health interfaces, doi: https://doi.org/10.1016/s2666-5247(23)00284-7
19. Wheeler NE, et al, 2023: Innovations in genomic antimicrobial resistance surveillance, doi: https://doi.org/10.1016/s2666-5247(23)00285-9
20. GLASS WGS for surveillance of AMR: https://www.who.int/publications/i/item/9789240011007
21. https://coursesandconferences.wellcomeconnectingscience.org/news_item/uniting-against- antimicrobial-resistance-in-africa-a-collaborative-effort-to-build-capacity-in-genomic-surveillance-of-amr/
22. https://www.flemingfund.org/publications/going-into-battle-future-of-pathogen-genomics-and-bioinformatics-in-africa-amr/