Skip to main content

Research Repository

Advanced Search

Defining the genes required for survival of Mycobacterium bovis in the bovine host offers novel insights into the genetic basis of survival of pathogenic mycobacteria

Gibson, Amanda J; Stiens, Jennifer; Passmore, Ian J; Faulkner, Valwynne; Miculob, Josephous; Willcocks, Sam; Coad, Michael; Berg, Stefan; Werling, Dirk; Wren, Brendan W; Nobeli, Irene; Villarreal-Ramos, Bernardo; Kendall, Sharon L

Authors

Amanda J Gibson

Jennifer Stiens

Ian J Passmore

Valwynne Faulkner

Josephous Miculob

Sam Willcocks

Michael Coad

Stefan Berg

Dirk Werling

Brendan W Wren

Irene Nobeli

Bernardo Villarreal-Ramos

Sharon L Kendall



Abstract

Tuberculosis has severe impacts in both humans and animals. Understanding the genetic basis of survival of both Mycobacterium tuberculosis, the human adapted species, and Mycobacterium bovis, the animal adapted species is crucial to deciphering the biology of both pathogens. There are several studies that identify the genes required for survival of M. tuberculosis in vivo using mouse models, however, there are currently no studies probing the genetic basis of survival of M. bovis in vivo. In this study we utilise transposon insertion sequencing in M. bovis to determine the genes required for survival in cattle. We identify genes encoding established mycobacterial virulence functions such as the ESX-1 secretion system, PDIM synthesis, mycobactin synthesis and cholesterol catabolism that are required in vivo. We show that, as in M. tuberculosis, phoPR is required by M. bovis in vivo despite the known defect in signalling through this system. Comparison to studies performed in glycerol adapted species such as M. bovis BCG and M. tuberculosis suggests that there are differences in the requirement for genes involved in cholesterol import (mce4 operon), oxidation (hsd) and detoxification (cyp125). We report good correlation with existing mycobacterial virulence functions, but also find several novel virulence factors, including genes involved in protein mannosylation, aspartate metabolism and glycerol-phosphate metabolism. These findings further extend our knowledge of the genetic basis of survival in vivo in bacteria that cause tuberculosis and provide insight for the development of novel diagnostics and therapeutics.

Citation

Gibson, A. J., Stiens, J., Passmore, I. J., Faulkner, V., Miculob, J., Willcocks, S., …Kendall, S. L. (2022). Defining the genes required for survival of Mycobacterium bovis in the bovine host offers novel insights into the genetic basis of survival of pathogenic mycobacteria. mBio, https://doi.org/10.1128/mbio.00672-22

Journal Article Type Article
Acceptance Date Jun 22, 2022
Publication Date Jul 14, 2022
Deposit Date Apr 23, 2022
Publicly Available Date Jul 19, 2022
Journal Mbio
Publisher American Society for Microbiology
Peer Reviewed Peer Reviewed
DOI https://doi.org/10.1128/mbio.00672-22
Additional Information This is a pre-submission acceptance review. However - mistakenly I forgot to put through the worktribe system before submission. It has been put out on a preprint server https://www.biorxiv.org/content/10.1101/2022.03.15.484275v2.full

Files





You might also like



Downloadable Citations