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

• DOI: 10.1038/s41591-021-01358-x
• Publication Date: 2021-05-24T16:03:06Z
• Authors: Sebastian M. Gygli; Chloé Loiseau; Levan Jugheli; Natia Adamia; Andrej Trauner; Miriam Reinhard; Amanda Ross; Sonia Borrell; Rusudan Aspindzel...; Nino Maghradze; Klaus Reither; Christian Beisel; Nestani Tukvadze; Zaza Avaliani; Sebastien Gagneux
• Keywords: 0301 basic medicine; 03 medical and health sciences; Drug Resistance, Multiple, Bacterial; Prisoners; Prisons; Mutation; Tuberculosis, Multidrug-Resistant; Antitubercular Agents; Humans; Mycobacterium tuberculosis; 3. Good health

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.