For #WorldAntimicrobialAwarenessWeek, we introduce our recent paper on antibiotic-resistant subpopulations in TB.
TB may be one of humanity’s oldest diseases, yet it still kills over 1M people yearly. As resistance spreads, knowing each patient’s resistance profile before treatment is vital. 🧬💊
Detecting minor resistance-associated variants in tuberculosis WGS samples improves the sensitivity of rifampicin resistance prediction:
doi.org/10.1093/jaca...
@philipwfowler.bsky.social @vbrunner.bsky.social #JACAMRNews #IDSky
Thanks Nicole! ☺️
😷 We also investigated the source of resistance in samples with resistant subpopulations using within-sample diversity, which suggests secondary infection events in at least 28% of samples.
⌛ Building on my previous work on compensatory mutations, we found that samples with resistant subpopulations were less likely to be compensated than homogeneous resistant samples, hinting at recent resistance acquisition.
📈 Relaxing the read support threshold, for example, can increase the sensitivity of rifampicin resistance prediction to over 95%.
Key take-aways:
🚧 In this work, we show that conservative parameters in bioinformatic pipelines can obscure resistant subpopulations in clinical samples of M. tb.
Our recent paper on rifampicin resistant subpopulations in M. tuberculosis (M. tb) has been published at JAC-antimicrobial resistance.
I am really happy to see this work published just hours before submitting my DPhil thesis! 🔗👇
doi.org/10.1093/jaca...
Come and work with me and use the 53,897 samples of M. tuberculosis we have collated to help tackle this important disease!
We are part of the OxCoD4TB consortium that is developing new therapeutics for tuberculosis.
Grade 7, funding until 28 Feb 2028, deadline noon Fri 4 July
bit.ly/4ndKOhF
@vbrunner.bsky.social doing her pitch for her poster at #ESMyco!
@modmedmicro.bsky.social
Having often grappled with the limited translational aspect of my pre-PhD work, the real-world impact of the topics discussed in this session and at this conference was refreshing and motivating and will help me push my PhD at @modmedmicro.bsky.social over the finish line later this year!
🚧 We showed that this issue can be easily mitigated by lowering the read support threshold required to call variants in whole-genome sequencing pipelines. This can lead to significantly increased sensitivity for rifampicin resistance prediction.
🧬 The talk allowed me to raise a central issue in sequencing-based diagnostics for M. tuberculosis: they often fail to detect resistant subpopulations - something that can have serious clinical implications.
Thrilled to have returned to the Congress of @escmid.bsky.social this year in the beautiful city of Vienna, and to have had the opportunity to present my latest work on rifampicin-resistant subpopulations in M. tuberculosis.
📋 Find all the details in our preprint: 🔗👇
www.biorxiv.org/content/10.1...
Another busy day at #ESCMIDGlobal!
0906 @vbrunner.bsky.social “RIF and subpopulations in TB”
0918 Ruan Spies “comparing TB pipelines" both in Hall 5
1000 Nicole Stoesser “plasmids & 1Health” in H2
1509 Jane Wei in Hall 2 “CAP and EHR”
P1405 - Valentina Pennetta
P2242 - Junko Takada
😷In a third of our clinical samples with resistant subpopulations, resistance was likely caused by a secondary infection instead of within-host evolution. Hence the patient contracted an M. tuberculosis infection at least twice, independently.
📈We managed to increase the sensitivity of rifampicin resistance prediction to over 95%, with no significant trade-off for specificity.
📢 Our preprint on rifampicin resistant subpopulations in clinical samples of M. tuberculosis has just been uploaded. We show how detection of resistant subpopulations can significantly improve WGS-based resistance prediction, and how they can help identify the source of resistance.
Check out @vbrunner.bsky.social latest work!
Just in time for #ESCMIDGlobal and her talk next Monday morning.
Our amazing @modmedmicro.bsky.social team, who are leading our efforts to tackle antimicrobial resistance #AMR – in the lab, with data and in software - went blue for this picture for #WAAW2024. See more about our research at bashthebug.net
Researchers in @modmedmicro.bsky.social are studying the DNA of bacteria to understand the genes they carry and how they are related. This can help us detect outbreaks and track how antimicrobial resistance genes spread, so we can contain them better #WAAW2024