2020): Coxiella effector protein CvpF subverts RAB26-dependent autophagy to promote vacuole biogenesis and virulence, Autophagy, ABSTRACT Coxiella burnetii, the etiological agent of the zoonosis Q fever, replicates inside host cells within a large vacuole displaying autolysosomal characteristics. The development of this compartment is mediated by bacterial effectors, which interfere with a number of host membrane trafficking pathways. By screening a Coxiella transposon mutant library, we observed that transposon insertions in cbu0626 led to intracellular replication and vacuole biogenesis defects. Here, we demonstrate that CBU0626 is a novel member of the Coxiella vacuolar protein (Cvp) family of effector proteins, which is translocated by the Dot/Icm secretion system and localizes to vesicles with autolysosomal features as well as Coxiellacontaining vacuoles (CCVs). We thus renamed this effector CvpF for Coxiella vacuolar protein F. CvpF specifically interacts with the host small GTPase RAB26, leading to the recruitment of the autophagosomal marker MAP1LC3B/LC3B (microtubule associated protein 1 light chain 3 beta) to CCVs. Importantly, cvpF::Tn mutants were highly attenuated compared to wild-type bacteria in the SCID mouse model of infection, highlighting the importance of CvpF for Coxiella virulence. These results suggest that CvpF manipulates endosomal trafficking and macroautophagy/autophagy induction for optimal C. burnetii vacuole biogenesis.
Co-evolution of bacterial pathogens with their hosts led to the emergence of a stunning variety of strategies aiming at the evasion of host defences, colonisation of host cells and tissues and, ultimately, the establishment of a successful infection. Pathogenic bacteria are typically classified as extracellular and intracellular; however, intracellular lifestyle comes in many different flavours: some microbes rapidly escape to the cytosol whereas other microbes remain within vacuolar compartments and harness membrane trafficking pathways to generate their host-derived, pathogen-specific replicative niche. Here we review the current knowledge on a variety of vacuolar lifestyles, the effector proteins used by bacteria as tools to take control of the host cell and the main membrane trafficking signalling pathways targeted by vacuolar pathogens as source of membranes and nutrients. Finally, we will also discuss how host cells have developed countermeasures to sense the biogenesis of the aberrant organelles harbouring bacteria. Understanding the dialogue between bacterial and eukaryotic proteins is the key to unravel the molecular mechanisms of infection and in turn, this may lead to the identification of new targets for the development of new antimicrobials.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.