GL09

Experimental studies show that antibiotic resistance causes replicative fitness costs that are modulated by the strain genetic background and compensatory evolution. How such epistatic interactions affect the transmission fitness of bacterial pathogens in humans, however, is unknown. Here we show that in the country of Georgia, multidrug-resistant Mycobacterium tuberculosis strains of lineage 4 (L4) transmit less than their drug-susceptible counterparts, whereas most multidrug-resistant strains of L2 suffer no such defect. Our findings further indicate that the high transmission fitness of these L2 strains results from epistatic interactions between the rifampicin resistance-conferring mutation RpoB S450L, compensatory mutations in the RNA polymerase and particular L2 genetic backgrounds. We conclude that the transmission of multidrug-resistant bacteria can be as efficient as drug-susceptible forms, which has important implications for the control of bacterial diseases.