Species-specific mechanisms of cytotoxicity toward immune cells determine the successful outcome of <i>Vibrio</i> infections

Abstract

<i>Vibrio</i> species cause infectious diseases in humans and animals, but they can also live as commensals within their host tissues. How <i>Vibrio</i> subverts the host defenses to mount a successful infection remains poorly understood, and this knowledge is critical for predicting and managing disease. Here, we have investigated the cellular and molecular mechanisms underpinning infection and colonization of 2 virulent <i>Vibrio</i> species in an ecologically relevant host model, oyster, to study interactions with marine <i>Vibrio</i> species. All <i>Vibrio</i> strains were recognized by the immune system, but only nonvirulent strains were controlled. We showed that virulent strains were cytotoxic to hemocytes, oyster immune cells. By analyzing host and bacterial transcriptional responses to infection, together with <i>Vibrio</i> gene knock-outs, we discovered that <i>Vibrio crassostreae</i> and <i>Vibrio tasmaniensis</i> use distinct mechanisms to cause hemocyte lysis. Whereas <i>V. crassostreae</i> cytotoxicity is dependent on a direct contact with hemocytes and requires an ancestral gene encoding a protein of unknown function, <i>r5.7</i>, <i>V. tasmaniensis</i> cytotoxicity is dependent on phagocytosis and requires intracellular secretion of T6SS effectors. We conclude that proliferation of commensal vibrios is controlled by the host immune system, preventing systemic infections in oysters, whereas the successful infection of virulent strains relies on <i>Vibrio</i> species-specific molecular determinants that converge to compromise host immune cell function, allowing evasion of the host immune system.