Ras GTPase-Like Protein MglA, a Controller of Bacterial Social-Motility in Myxobacteria, Has Evolved to Control Bacterial Predation by Bdellovibrio

Abstract

Bdellovibrio bacteriovorus invade Gram-negative bacteria in a predatory process requiring Type IV pili (T4P) at a single invasive pole, and also glide on surfaces to locate prey. Ras-like G-protein MglA, working with MglB and RomR in the deltaproteobacterium Myxococcus xanthus, regulates adventurous gliding and T4P-mediated social motility at both M. xanthus cell poles. Our bioinformatic analyses suggested that the GTPase activating protein (GAP)-encoding gene mglB was lost in Bdellovibrio, but critical residues for MglABd GTP-binding are conserved. Deletion of mglABd abolished prey-invasion, but not gliding, and reduced T4P formation. MglABd interacted with a previously uncharacterised tetratricopeptide repeat (TPR) domain protein Bd2492, which we show localises at the single invasive pole and is required for predation. Bd2492 and RomR also interacted with cyclic-di-GMP-binding receptor CdgA, required for rapid prey-invasion. Bd2492, RomRBd and CdgA localize to the invasive pole and may facilitate MglA-docking. Bd2492 was encoded from an operon encoding a TamAB-like secretion system. The TamA protein and RomR were found, by gene deletion tests, to be essential for viability in both predatory and non-predatory modes. Control proteins, which regulate bipolar T4P-mediated social motility in swarming groups of deltaproteobacteria, have adapted in evolution to regulate the anti-social process of unipolar prey-invasion in the “lone-hunter” Bdellovibrio. Thus GTP-binding proteins and cyclic-di-GMP inputs combine at a regulatory hub, turning on prey-invasion and allowing invasion and killing of bacterial pathogens and consequent predatory growth of Bdellovibrio.

Cell-cycle progress in obligate predatory bacteria is dependent upon sequential sensing of prey recognition and prey quality cues

“…It was proposed recently that Bd0108 controls the extrusion/ retraction of a type IVa pilus in B. bacteriovorus (52) that is essential for predation and prey entry but is not involved in prey attachment (53)(54)(55). Recognition thus includes signaling and stable attachment, and both processes are sustained by prey ghosts.…”

“…When an AP cell stably binds to a prey cell through a still unknown mechanism, concomitant sensing of the first cue, located in the cytoplasmic membrane (54), alleviates Bd0108 inhibition, altering the extrusion/retraction state of the type IVa pilus found at the nonflagellated, invasive pole with which Bd0108 is associated (52), leading to signal transduction. This process may be mediated, at least in part, through CdgA, a cyclic di-GMP effector required for efficient penetration of the prey cell (57) that interacts with the pilus' regulatory protein complex (55). The cyclic di-GMP machinery is essential for both prey entry and progeny escape at the end of the predator's replicative cycle (57), indicating that this second messenger is involved in transducing the first cue.…”

“…As a result, the inhibition by Bd0108 is alleviated, setting off signal transduction, possibly in part through CdgA, a cyclic di-GMP effector required for efficient penetration to the prey cell. CdgA interacts with the pilus' regulatory protein complex (55). Early sensing induces the recognition program: bd0108 is completely silenced, and merRNA levels decline, but the σ 28 regulon remains active, and the bdelloplast-formation genes and the early GP genes are induced, enabling penetration and bdelloplast formation as well as the production of growth-related functions.…”

Bdellovibrioet organismes apparentés

“…Il est formé d'une partie SYNTHÈSE REVUES de la proie. Le premier signal est vraisemblablement lié au contact établi entre le pilus, situé au niveau du pôle d'invasion du prédateur, et la proie [28]. Les seconds dépendent de la fonction de dégradation des ARN [16].…”

“…Les seconds dépendent de la fonction de dégradation des ARN [16]. Le pilus pourrait interagir avec le complexe protéique du pôle d'invasion constitué entre autres, de la protéine RomR (required for motility response regulator) [28] qui interagit avec CdgA (cyclic-di-GMP diguanylate cyclase), une protéine possédant un domaine de signalisation GGDEF dégénéré [29] dont une mutation ralentit la formation du bdelloplaste. CdgA fait partie du système de signalisation du messager secondaire di-GMP cyclique qui impacte fortement le phénotype de B. bacteriovorus et contrôle l'aiguillage entre prédation et croissance HI [29].…”