Genes required for mycobacterial growth defined by high density mutagenesis

TLDR

Tuberculosis remains a leading cause of infectious death worldwide despite extensive research. The study aims to identify genes essential for Mycobacterium tuberculosis growth to uncover new antimicrobial targets. The authors used transposon site hybridization (TraSH) to map genes required for optimal growth of Mycobacterium tuberculosis. The analysis revealed a set of growth‑required genes, many of unknown function, largely conserved in Mycobacterium leprae yet with a high proportion lacking orthologues in other bacteria, indicating variable minimal gene sets across species.

Abstract

Summary Despite over a century of research, tuberculosis remains a leading cause of infectious death worldwide. Faced with increasing rates of drug resistance, the identification of genes that are required for the growth of this organism should provide new targets for the design of antimycobacterial agents. Here, we describe the use of transposon site hybridization (TraSH) to comprehensively identify the genes required by the causative agent, Mycobacterium tuberculosis , for optimal growth. These genes include those that can be assigned to essential pathways as well as many of unknown function. The genes important for the growth of M. tuberculosis are largely conserved in the degenerate genome of the leprosy bacillus, Mycobacterium leprae , indicating that non‐essential functions have been selectively lost since this bacterium diverged from other mycobacteria. In contrast, a surprisingly high proportion of these genes lack identifiable orthologues in other bacteria, suggesting that the minimal gene set required for survival varies greatly between organisms with different evolutionary histories.