Bacterial type VI secretion system facilitates niche domination

Over the last few decades humanity has experienced a series of tremendous technological advances, especially in the realm of basic science. A plethora of new approaches has allowed us to appreciate life in previously unimaginable detail, prompting the realization that life in the microscopic world is not so different from what we can observe with our naked eyes. Microorganisms, for instance, like any other organism, compete with one another for resources and space. Bacteria often use simple mechanisms to occupy their niche such as rapid growth and biofilm formation. Bacteria also use ingenious strategies to maximize their success. Indeed, to engage in warfare, microorganisms often produce diffusible toxic antimicrobial compounds as well as other more complicated molecular weapons. Secretion systems are a particular kind of molecular weapon as they release or inject molecules and substrates that interact not only with hosts and predators but also with bacterial competitors. Given that the type VI secretion system (T6SS) has been recognized as a frequently used molecular weapon, it is not at all surprising that it is found widely distributed throughout diverse bacterial species (around 25% of all gram-negatives) (1). The T6SS system was discovered in Vibrio cholerae due to its toxicity against the social amoeba Dictyostelium discoideum (2). That same year, it was also suggested to contribute to the pathogenesis of Pseudomonas aeruginosa in cystic fibrosis patients (3). Follow-up studies showed that the T6SS of these two species could also be used against other bacteria (4, 5). Indeed, while being recognized for its involvement in host–pathogen and predator–prey interactions, the principal role of the T6SS is currently thought to be as an antibacterial weapon. In PNAS, Speare et al. (6) explore an accessory T6SS of the symbiotic bacterium Vibrio fischeri and describe how this T6SS contributes to light-organ occupancy within the squid host.

PAAR-repeat proteins sharpen and diversify the type VI secretion system spike

Sergii Buth, Petr Leiman

The bacterial type VI secretion system (T6SS) is a large multicomponent, dynamic macromolecular machine that has an important role in the ecology of many Gram-negative bacteria. T6SS is responsible for translocation of a wide range of toxic effector molecules, allowing predatory cells to kill both prokaryotic as well as eukaryotic prey cells(1-5). The T6SS organelle is functionally analogous to contractile tails of bacteriophages and is thought to attack cells by initially penetrating them with a trimeric protein complex called the VgrG spike(6,7). Neither the exact protein composition of the T6SS organelle nor the mechanisms of effector selection and delivery are known. Here we report that proteins from the PAAR (proline-alanine-alanine-arginine) repeat superfamily form a sharp conical extension on the VgrG spike, which is further involved in attaching effector domains to the spike. The crystal structures of two PAAR-repeat proteins bound to VgrG-like partners show that these proteins sharpen the tip of the T6SS spike complex. We demonstrate that PAAR proteins are essential for T6SS-mediated secretion and target cell killing by Vibrio cholerae and Acinetobacter baylyi. Our results indicate a new model of the T6SS organelle in which the VgrG-PAAR spike complex is decorated with multiple effectors that are delivered simultaneously into target cells in a single contraction-driven translocation event.

Nature Publishing Group2013

Two nanomachines drive evolution in diverse Vibrio species

Noémie Matthey

Horizontal gene transfer (HGT) has a major impact on bacterial evolution, leading to acquisition or deletion of genes and gene clusters, including those encoding antibiotic resistances and virulence factors. HGT therefore contributes to pathogen emergence, which can have a major impact on human health. As a mode of HGT, natural competence for transformation allows bacteria to directly acquire DNA from the environment and to integrate parts of this genetic material within their genomes. The human pathogen Vibrio cholerae is naturally competent when it grows in association with the chitinous exoskeletons of zooplankton. Under this condition, the competence state is initiated by the regulatory protein TfoX, which co-induces a molecular killing device known as the type VI secretion system (T6SS). The co-regulation of the T6SS and competence results in the lysis of non-immune neighboring bacteria and the subsequent acquisition of their DNA, which fosters HGT. In V. cholerae, the T6SS is also activated by the TfoX homologue protein, named TfoY. In this study, we aimed at studying the regulatory pathways and the co-regulation of interbacterial predation and DNA uptake in order to provide new insights into the environmental lifestyle of V. cholerae and other vibrios. We first investigated the conserved function of TfoX- and TfoY in V. fischeri, V. alginolyticus, and V. parahaemolyticus using diverse methods such as qRT-PCR, interbacterial killing assays, and motility assessments. We demonstrated that TfoX-mediated T6SS and competence induction and TfoY-induced motility are conserved phenotypes in the tested Vibrio species, whereas the TfoY-mediated T6SS regulation varied. These variations might reflect diverse defense mechanisms, as these different species have adapted to cope with their environmental niches. Next, we tested the outcome of the TfoX-mediated co-regulation of the T6SS and competence in V. cholerae. Under conditions mimicking the bacteriumâs natural habitat, we showed for the first time the extent of DNA that was integrated on V. choleraeâs genome after T6SS-mediated interbacterial predation. Indeed, we demonstrated that T6SS-dependent bacterial predation not only increased the transformation rates but also fostered the exchange of multiple and huge fragments of DNA. We also showed the necessity of an exquisite co-regulation between the T6SS, the competence-related DNA uptake machinery, and the competence-repressed nuclease. Finally, we disclosed that prey-released DNA is not a private good of the attacking bacterium but also accessible to other surrounding cells that have likewise entered the competence state. Altogether, our findings shed light on the conservation of the TfoX- and TfoY-driven phenotypes in several Vibrio species. We also contributed to a better understanding of the interplay between neighbor predation and DNA uptake and the consequences that this interplay has on genome plasticity.

EPFL2019

Two nanomachines drive evolution in diverse Vibrio species

Noémie Matthey

EPFL2019