RNase E and HupB dynamics foster mycobacterial cell homeostasis and fitness

Anna Griego; Thibaut Douché; Quentin Giai Gianetto; Mariette Matondo; Giulia Manina

doi:10.1016/j.isci.2022.104233

RNase E and HupB dynamics foster mycobacterial cell homeostasis and fitness

iScience. 2022 Apr 12;25(5):104233. doi: 10.1016/j.isci.2022.104233. eCollection 2022 May 20.

Authors

Anna Griego¹, Thibaut Douché², Quentin Giai Gianetto^{2

3}, Mariette Matondo², Giulia Manina¹

Affiliations

¹ Institut Pasteur, Université de Paris, Microbial Individuality and Infection Group, F-75015 Paris, France.
² Institut Pasteur, CNRS USR 2000, Mass Spectrometry for Biology Unit, F-75015 Paris, France.
³ Institut Pasteur, CNRS USR 3756, Bioinformatics and Biostatistics HUB, F-75015 Paris, France.

Abstract

RNA turnover is a primary source of gene expression variation, in turn promoting cellular adaptation. Mycobacteria leverage reversible mRNA stabilization to endure hostile conditions. Although RNase E is essential for RNA turnover in several species, its role in mycobacterial single-cell physiology and functional phenotypic diversification remains unexplored. Here, by integrating live-single-cell and quantitative-mass-spectrometry approaches, we show that RNase E forms dynamic foci, which are associated with cellular homeostasis and fate, and we discover a versatile molecular interactome. We show a likely interaction between RNase E and the nucleoid-associated protein HupB, which is particularly pronounced during drug treatment and infection, where phenotypic diversity increases. Disruption of RNase E expression affects HupB levels, impairing Mycobacterium tuberculosis growth homeostasis during treatment, intracellular replication, and host spread. Our work lays the foundation for targeting the RNase E and its partner HupB, aiming to undermine M. tuberculosis cellular balance, diversification capacity, and persistence.

Keywords: Biological sciences; Ecology; Environmental science; Microbiology.