Phenotypic heterogeneity is an essential strategy evolved by bacteria to survive and rapidly adapt to fluctuating environments or stresses such as those encountered during infection. This heterogeneity, whether arising from stochastic gene expression or triggered by environmental stresses, enables clonal bacterial subpopulations to dynamically modulate gene expression. In pathogenic bacteria, such adaptability helps to evade the host immune responses, resist antibiotic treatments and persist in the host in a latent state.
Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis, which remains a major global health threat due to its high pathogenicity, is a good example of this adaptation. Indeed, Mtb is known to survive antibiotic treatments and persist for extended periods of time in its host, often leading to relapse and therapeutic failure. Underlining this is Mtb’s ability to generate phenotypically heterogenous subpopulations able to withstand a wide array of stresses during infection.
Previous studies showed that GroEL2, a mycobacterial chaperonin of the heat-shock protein family, can be cleaved by the Hip1 protease, changing its conformation from a highly immunogenic multimeric form to a monomeric state, which dampens the innate immune response. Molecular signaling at the origin of GroEL2 cleavage and therefore variation in the host innate immune response are yet to be determined, as well as the consequences of GroEL2 cleavage on its interaction with putative host proteins.
As such, we aim to further dissect the molecular mechanisms behind the immunomodulatory effects of GroEL2 during infection. Indeed, understanding this dynamic host-pathogen interaction could provide novel insights into bacterial adaptation as well as potentially identify novel therapeutic targets for improving tuberculosis treatment and decreasing tissue pathology.
