How do changes in antibiotic use, various pathways to resistance, multiple drug resistance, and more come together to shape the success and failure of bacterial lineages in a real-world epidemic? #AMR #microsky A preprint: www.biorxiv.org/content/10.1... (1/15) - ThreadSky

dhelekal.bsky.social • 20 days ago

How do changes in antibiotic use, various pathways to resistance, multiple drug resistance, and more come together to shape the success and failure of bacterial lineages in a real-world epidemic? #AMR #microsky
A preprint: https://www.biorxiv.org/content/10.1101/2025.02.03.636319v2
(1/15)

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dhelekal.bsky.social•20 days ago

How much of lineage growth and contraction is attributable to the resistance determinants they carry and those determinants’ fitness costs/benefits?
(2/15)

dhelekal.bsky.social•20 days ago

Answering these questions is difficult. In bacteria, lineage dynamics can be influenced by complex life cycles, host immune pressures, population structures, and other factors. We also often lack sufficient sampling of bacterial isolates, let alone information on antibiotic exposure.
(3/15)

dhelekal.bsky.social•20 days ago

We overcame these challenges by studying the Neisseria gonorrhoeae epidemic in the US. This has many advantages.

Figure Source: Centers for Disease Control and Prevention. Gonococcal Isolate Surveillance Project (GISP) Profiles, 2022. (4/15)

dhelekal.bsky.social•20 days ago

1. A large collection of sequenced clinical isolates spanning 20 years.
2. Well characterized genetic pathways to antibiotic resistance.
3. Nationwide antibiotic treatment data (as above).
4. A species that is an obligate human pathogen that does not elicit a protective immune response.
(5/15)

dhelekal.bsky.social•20 days ago

Our strategy was to define lineages based on AMR determinants and then use phylodynamic modelling to investigate their success and failure over time as treatment changed. An exploratory analysis of a cluster of lineages suggested an alignment between the eff. pop. size and treatment changes.
(6/15)

dhelekal.bsky.social•20 days ago

We formalized this notion in a hierarchical Bayesian model that lends itself to incorporating variation across lineages, lineage backgrounds effects, and resistance determinants. We then estimated the fitness impacts of resistance determinants and how these changed over time.
(7/15)

typemat12.bsky.social•20 days ago

Looks great David, can't wait to read it.

dhelekal.bsky.social•20 days ago

Thanks, Mat!

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