Virulence determinants for Vibrio parahaemolyticus infection
Highlights
► V. para. is a marine bacterium associated with seafood poisoning. ► V. para. utilizes virulence factors to cause both cytotoxicity and invasive enterotoxicity. ► Virulence factors includes toxins, an adhesin and type III secretion systems. ► Characterizing virulence factors results in novel insights into host signaling. ► Studies on V. para. enrich the understanding of host–pathogen interactions.
Introduction
Vibrio parahaemolyticus is a Gram-negative, halophilic bacterium that inhabits marine or estuarine environments and causes acute gastroenteritis associated with consumption of raw or undercooked seafood [1, 2]. In rare cases, V. para. causes wound infections or septicemia and the latter is correlated with a high mortality rate [3]. This bacterium was first discovered in 1950 by Tsunesaburo Fujino of Osaka University after a seafood poisoning outbreak in Japan [4]. Since its discovery, V. para. has been found to be a bacterial pathogen that causes gastroenteritis throughout the world [4, 5].
V. para. possesses a wide variety of virulence factors, including a newly discovered adhesin, toxins, and secreted effectors involved in attachment, cytotoxicity and enterotoxicity [6]. It inhabits marine or estuarine environments, where it is able to persist and proliferate [4, 5]. Although the natural host for this pathogen is unknown, protozoa and/or shellfish are possible candidates [5, 7, 8]. Since bacterial virulence factors normally have evolutionarily conserved targets, such as small regulatory GTPases and MAP kinase signaling pathways, V. para. is also able to invade and cause diseases in an incidental human host [9]. Identifying and characterizing its many virulence factors has provided novel insights not only into the molecular mechanisms utilized by bacterial pathogens to survive in animal hosts, but also into biochemical signaling mechanism used throughout nature. Herein, we describe some of the recent contributions made toward understanding V. para. pathogenesis, including studies on quorum and surface sensing, adhesins, toxins, and its two Type 3 Secretion Systems, T3SS1 and T3SS2 (Table 1, Figure 1).
Section snippets
Quorum sensing and surface sensing
Although there is no conclusive evidence between quorum sensing (QS) and bacterial virulence for V. para., QS is an important feature in the life style of V. para., and therefore, may play a role in pathogen survival and proliferation. Bacterial QS is a system of stimulation and response based on population density, resulting in cell-to-cell communication by secreted signaling molecules [10, 11]. These signaling molecules, termed ‘auto-inducers’, bind to membrane localized receptor proteins on
Virulence factors encoded by Vibrio parahaemolyticus
V. para. strains encode a number of different virulence factors, including adhesins, thermostable direct hemolysin (TDH) and TDH related hemolysin (TRH) and two Type 3 Secretion Systems, T3SS1 and T3SS2 [20]. All V. para. strains encode T3SS1, which is implicated in survival of this bacteria in the environment, although the natural host(s) is(are) unknown [20, 21, 22•]. The T3SS1 contains a number of virulence factors that cause efficient lysis of an infected host cell and allow for the release
MAM7, a shared adhesin
During infection, the initial contact and anchoring of bacteria to a host cell are essential for the activation and delivery of later virulence factors. Adhesins are bacterial proteins that are present at the bacterial surface or released into extracellular space to form a contact platform for bacterial attachment onto a host cell. The V. para. multivalent adhesion molecule, MAM7, was identified to be critical for the initial attachment of bacteria to eukaryotic cells during the early stages of
TDH and TRH toxins
TDH and TRH, the first studied V. para. virulence factors, were identified in the 1980s and found to cause a hemolytic reaction on Wagatsuma's medium, a type of blood agar used to identify V. para. strains containing these toxins [4]. All clinically isolated V. para. strains possess TDH and/orTRH [4, 21]. The pathogenic strain RIMD 2210633 contains two copies of TDH (TDHA/S) that are encoded and co-regulated with the T3SS2 genes on its second chromosome [28].
TDH forms a tetramer in solution
Type III secretion system 1 (T3SS1)
T3SSs are needle-like bacterial machinery used to inject bacterial proteins called effectors directly into the membrane and cytoplasm of eukaryotic cells [38]. The T3SS apparatus consists of a basal body spanning the bacterial inner and outer membranes, a needle that is polymerized and extended into extracellular space, and a tip complex that resides at the top of the needle and is likely to be involved in T3SS activation [39, 40]. T3SSs allow bacterial effectors to be delivered directly into
Type III secretion system 2 (T3SS2)
Clinical isolates and some environmental strains of V. para. contain the T3SS2 encoded on a pathogenicity island on chromosome 2 [20, 21, 22•]. Initially, T3SS2 was observed to cause changes in morphology in HeLa cells, weak cytotoxicity in Caco-2 cells, and enterotoxicity in the rabbit ileal loop model, infant rabbits and piglets [32, 35•, 36, 52, 53]. Honda and colleagues discovered that treatment with bile salts caused the transcriptional regulator VtrA to initiate the expression of VtrB,
Conclusion
Significant progress has been made regarding the identification and characterization of different V. para. virulence factors. Despite that, how the different virulence factors are correlated and the order of delivery into host cells is still not known. While T3SS2 has been known to be responsible for enterotoxicity for some time, new data on VopC indicating its role in invasion, combined with its conservation in V. cholerae, a new perspective on the role of T3SS2 during infection is presented [
Competing interest
The authors declare that no competing interests exist.
References and recommended reading
Papers of particular interest, published within the period of review, have been highlighted as:
• of special interest
•• of outstanding interest
Acknowledgements
Thanks to the Orth Lab for the editing and insightful comments. K.O. and L.Z. are supported by National Institutes of Health-AID Grant R01-AI056404 and Grant I-1561 from the Welch Research Foundation. K.O. is a Burroughs Welcome Investigator in Pathogenesis of Infectious Disease and a W.W. Caruth, Jr. Biomedical Scholar.
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