TheVibrio choleraeType VI Secretion System Can Modulate Host Intestinal Mechanics to Displace Commensal Gut Bacteria

Abstract

Host-associated microbiota help defend against bacterial pathogens; the mechanisms that pathogens possess to overcome this defense, however, remain largely unknown. We developed a zebrafish model and used live imaging to directly study how the human pathogen Vibrio cholerae invades the intestine. The gut microbiota of fish mono-colonized by commensal strain Aeromonas veronii was displaced by V. cholerae expressing its Type VI Secretion System (T6SS), a syringe-like apparatus that deploys effector proteins into target cells. Surprisingly, displacement was independent of T6SS-mediated killing of Aeromonas, driven instead by T6SS-induced enhancement of zebrafish intestinal movements that led to expulsion of the resident commensal by the host. Deleting an actin crosslinking domain from the T6SS apparatus returned intestinal motility to normal and thwarted expulsion, without weakening V. cholerae's ability to kill Aeromonas in vitro. Our finding that bacteria can manipulate host physiology to influence inter-microbial competition has implications for both pathogenesis and microbiome engineering.

The Bacterial Enhancer Binding Protein VasH Promotes Expression of a Type VI Secretion System in Vibrio fischeri during Symbiosis

“…Using genetic approaches to interrogate regulation of the T6SS in V. fischeri, we have found that the T6SS is positively regulated by 54 and the bEBP VasH during symbiosis. The role and prevalence of the T6SS in beneficial bacteria is an emerging field of study that is revealing the impact of the T6SS weapon on microbiota composition and assembly (12,42,43). A current obstacle to understanding how the T6SS affects the assembly of symbiont populations within a host ecosystem has been the inability to study the factors that regulate these nanomachines during symbiosis establishment.…”

From Welfare to Warfare: The Arbitration of Host-Microbiota Interplay by the Type VI Secretion System

“…The T6SS yielded by bacterial pathogens targeting host cells presents a further risk to the microbiota, since the ensuing subversion of host processes affects their ecological niche. Indeed, such indirect impact has been demonstrated in the zebrafish model of cholera, where the actin-crosslinking domain of VgrG1 of V. cholerae stimulates peristalsis, resulting in the collapse of the resident microbial community (Logan et al, 2018). The gradual repopulation by the commensal microbiota may evict the invading pathogen despite the reversal of the numerical advantage; yet the niche must still be conducive for this repopulation to occur.…”

Mapping the microbiome location helps elucidate its role

“…To study the basic principles of how microbes interact with one another and the host, Parthasarathy's team populates a sterile zebrafish gut with only a couple species. For example, in a study published earlier this year, they showed how the cholera virus might infect its host (8). After colonizing an otherwise sterile zebrafish gut with a bacterium called Aeromonas veronii, the researchers introduced the cholera virus, discovering that the virus induces the gut to contract, which expels the bacterium and enables the virus to take over.…”