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Prisons as ecological drivers of fitness-compensated multidrug-resistant Mycobacterium tuberculosis

Sebastian M. Gygli, Chloé Loiseau, Levan Jugheli, Natia Adamia, , Miriam Reinhard, , Sonia Borrell, Rusudan Aspindzelashvili, Nino Maghradze,
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Published: 24 May 2021
Nature Medicine pp 1-7; doi:10.1038/s41591-021-01358-x

Abstract: Multidrug-resistant tuberculosis (MDR-TB) accounts for one third of the annual deaths due to antimicrobial resistance1. Drug resistance-conferring mutations frequently cause fitness costs in bacteria2–5. Experimental work indicates that these drug resistance-related fitness costs might be mitigated by compensatory mutations6–10. However, the clinical relevance of compensatory evolution remains poorly understood. Here we show that, in the country of Georgia, during a 6-year nationwide study, 63% of MDR-TB was due to patient-to-patient transmission. Compensatory mutations and patient incarceration were independently associated with transmission. Furthermore, compensatory mutations were overrepresented among isolates from incarcerated individuals that also frequently spilled over into the non-incarcerated population. As a result, up to 31% of MDR-TB in Georgia was directly or indirectly linked to prisons. We conclude that prisons fuel the epidemic of MDR-TB in Georgia by acting as ecological drivers of fitness-compensated strains with high transmission potential. Understanding the ecological drivers of highly transmissible, multidrug-resistant Mycobacterium tuberculosis.
Keywords: MDR TB / evolution / incarcerated / ecological / prisons / compensatory / fitness compensated

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