Genetic analysis of Vibrio parahaemolyticus intestinal colonization

Abstract

Vibrio parahaemolyticus is the most common cause of seafood-borne gastroenteritis worldwide and a blight on global aquaculture. This organism requires a horizontally acquired type III secretion system (T3SS2) to infect the small intestine, but knowledge of additional factors that underlie V. parahaemolyticus pathogenicity is limited. We used transposon-insertion sequencing to screen for genes that contribute to viability of V. parahaemolyticus in vitro and in the mammalian intestine. Our analysis enumerated and controlled for the host infection bottleneck, enabling robust assessment of genetic contributions to in vivo fitness. We identified genes that contribute to V. parahaemolyticus colonization of the intestine independent of known virulence mechanisms in addition to uncharacterized components of T3SS2. Our study revealed that toxR, an ancestral locus in Vibrio species, is required for V. parahaemolyticus fitness in vivo and for induction of T3SS2 gene expression. The regulatory mechanism by which V. parahaemolyticus ToxR activates expression of T3SS2 resembles Vibrio cholerae ToxR regulation of distinct virulence elements acquired via lateral gene transfer. Thus, disparate horizontally acquired virulence systems have been placed under the control of this ancestral transcription factor across independently evolved human pathogens.Vibrio parahaemolyticus | transposon-insertion sequencing | type III secretion | bacterial pathogenesis | pathogen evolution T he gram-negative γ-proteobacterium Vibrio parahaemolyticus thrives in either pathogenic or symbiotic association with marine organisms and as a planktonic bacterium (1). This facultative human pathogen, abundant in aquatic environments, was first isolated following a food poisoning outbreak in 1952 and has emerged as the leading cause of seafood-associated gastroenteritis worldwide and a blight on global aquaculture (2, 3). Sequencing of the V. parahaemolyticus genome and the development of animal models of infection have demonstrated a critical role for type III secretion in V. parahaemolyticus virulence (4, 5).Pathogenic isolates of V. parahaemolyticus encode two type III secretion systems (T3SSs), which are multiprotein structures that mediate the translocation of bacterial effector proteins directly into eukaryotic cells (4, 6). All V. parahaemolyticus strains encode a T3SS on the large chromosome (T3SS1), and the vast majority of clinical isolates, but few environmental isolates possess a horizontally acquired pathogenicity island (VPaI-7) encoding a second T3SS (T3SS2) and one or more pore-forming toxins (TDH) (7). Studies using the infant rabbit model of V. parahaemolyticus infection, which recapitulates manifestations of human gastrointestinal disease (e.g., profuse diarrhea, enteritis, epithelial disruption), revealed that although T3SS1 and TDH are dispensable for intestinal colonization and pathogenesis, colonization and pathology are dependent on T3SS2, consistent with the epidemiological association between T3SS2 and pathogenicity (5). Furthermor...

Complete genome of Vibrio parahaemolyticus FORC014 isolated from the toothfish

“…Moreover, we defined T3SS1 and T3SS2 genes in our strain using the BLAST method, which produced the same result. T3SS2 has been described as a major essential factor for enterotoxicity and intestinal colonization [8, 25]. Particularly, the vopB2 (FORC14_1152) gene was detected in this T3SS2 region on chromosome 1.…”

Large-scale seaweed cultivation diverges water and sediment microbial communities in the coast of Nan'ao Island, South China Sea

“…For example, Peredibacter (Lu and Cai, 2010) was shown to control the growth of one kind of fish pathogen Typhimurium. Also, some potential pathogens, such as Vibrio (Austin and Zhang, 2006;Hubbard et al, 2016) and Arcobacter (Lehner et al, 2005) were abundant at CZ but not GZ sediments. Such a divergence in abundant genera could be explained by different environmental properties such as lower nutrients and higher algal polysaccharide at GZ, implying a healthier community composition at the seaweed cultivation zone.…”

Parallel Evolution of Two Clades of an Atlantic-Endemic Pathogenic Lineage of Vibrio parahaemolyticus by Independent Acquisition of Related Pathogenicity Islands

“…Two evolutionarily divergent horizontally acquired accessory systems (T3SS2␣ and T3SS2␤) contribute to human disease and are genetically linked to hemolysin genes (two tdh genes with T3SS2␣, and trh with T3SS2␤) in contiguous but distinct islands (4,(15)(16)(17). The first described tdh-harboring island (called by several different names including Vp-PAI [15], VPaI-7 [4], and tdhVPA [17]) from an Asian pandemic strain called RIMD 2210366 is fairly well characterized (4,5,13,18,19). In contrast, islands containing T3SS2␤ linked to trh and a urease (ure) cluster, which confers a useful diagnostic phenotype, (where similar islands are described by others as Vp-PAI TH3966 [16] or trhVPA [17,20]) have received only modest attention.…”