The role of RNase J in drug resistance in mycobacteria

MARTINI MARÍA CARLA; HICKS NATHAN; ZHAO YANLIN; YANG JIAN; FORTUNE SARAH; SHELL SCARLET

Boston

Congreso; Boston Bacterial meeting; 2017

Harvard University

Tuberculosis (TB) is a disease of global concern caused by the bacterium Mycobacterium tuberculosis (MTB). Emergence of multidrug-resistant (MDR) TB strains has become a major health challenge worldwide. Drug resistance in MTB is mainly attributed to mutations in the genes encoding drug targets or enzymes required for drug activation. However, recent studies have reported that a percentage of MDR isolates contain mutations in other genes in addition to the expected target and activator mutations (1). These findings suggest that other players could be involved in the development of drug resistance. Among these genes is Rv2752c, encoding RNase J, a ribonuclease that is not essential for mycobacterial growth. Mutations in Rv2752c were reported to be associated with drug resistance in a collection of clinical isolates (1). In this work, we present data showing changes in susceptibility to rifampicin and isoniazid as well as to other antibiotics when the gene encoding RNase J is deleted or overexpressed in Mycobacterium smegmatis. In addition, RNA-seq data revealed that a number of genes are up- and down-regulated when RNase J is absent or overexpressed in both M. smegmatis and M. tuberculosis.Together, our results support the hypothesis that RNase J is involved in development of drug resistance in mycobacteria by a mechanism still unknown. The study of this particular gene as well as others identified in MDR isolates can contribute to understanding the basis of resistance in mycobacteria and help to develop new strategies to efficiently treat TB.Reference: 1. Zhang, H, et al. (2013). Nature Genetics, 45(10), 1255?1260.