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Clinical isolates of Mycobacterium tuberculosis with increased rates of error in gene translation (mistranslation) involving the indirect tRNA-aminoacylation pathway have increased tolerance to the first-line antibiotic rifampicin. Here, we identify that the aminoglycoside kasugamycin can specifically decrease mistranslation due to the indirect tRNA pathway. Kasugamycin but not the aminoglycoside streptomycin, can limit emergence of rifampicin resistance in vitro and increases mycobacterial susceptibility to rifampicin both in vitro and in a murine model of infection. Moreover, despite parenteral administration of kasugamycin being unable to achieve the in vitro minimum inhibitory concentration, kasugamycin alone was able to significantly restrict growth of Mycobacterium tuberculosis in mice. These data suggest that pharmacologically reducing mistranslation may be a novel mechanism for targeting bacterial adaptation.<\/jats:p>","DOI":"10.7554\/elife.36782","type":"journal-article","created":{"date-parts":[[2018,8,28]],"date-time":"2018-08-28T08:07:01Z","timestamp":1535443621000},"source":"Crossref","is-referenced-by-count":44,"title":["Kasugamycin potentiates rifampicin and limits emergence of resistance in Mycobacterium tuberculosis by specifically decreasing mycobacterial mistranslation"],"prefix":"10.7554","volume":"7","author":[{"given":"Swarnava","family":"Chaudhuri","sequence":"first","affiliation":[{"name":"Centre for Global Health and Infectious Diseases, Collaborative Innovation Centre for the Diagnosis and Treatment of Infectious Diseases, Tsinghua University School of Medicine, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liping","family":"Li","sequence":"additional","affiliation":[{"name":"Public Health Research Institute, New 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