Ribosome profiling in<i>Mycobacterium tuberculosis</i>reveals robust leaderless translation

<jats:title>Abstract</jats:title><jats:p><jats:italic>Mycobacterium tuberculosis</jats:italic>, which causes tuberculosis, expresses a large proportion of leaderless transcripts lacking the canonical bacterial translation initiation signals. The role leaderless genes play in the physiology of this pathogen, which can undergo prolonged periods of non-replicating persistence in the host, is currently unknown. We have previously demonstrated that levels of leaderless transcription increase under conditions of nutrient starvation. However, little is known about the implications of this for persistent infection. Here, we performed ribosome profiling to characterise the translational landscape of<jats:italic>M. tuberculosis in vitro</jats:italic>. Our data reveals robust leaderless translation in the pathogen and points towards different mechanisms for their initiation of translation compared to canonical Shine-Dalgarno genes. Furthermore, under conditions of nutrient starvation, we found a significant global up-regulation of leaderless genes in the translatome. Our data represents a rich resource for others seeking to understand translational regulation not only in<jats:italic>M. tuberculosis</jats:italic>but in bacterial pathogens.</jats:p>