The MSHA pilus of Vibrio parahaemolyticus has lectin functionality and enables TTSS-mediated pathogenicity

O’Boyle, Nicky; Houeix, Benoit; Kilcoyne, Michelle; Joshi, Lokesh; Boyd, Aoife

doi:10.1016/j.ijmm.2013.07.010

Cited by 45 publications

(64 citation statements)

References 43 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Sulfated GAGs promoted V. parahaemolyticus adhesion even when GAGs were not covalently bound to host cells; however, bacterial adhesion and associated cytotoxicity were blocked by the presence of excess sulfated GAGs, which likely serve as competitive inhibitors. The bacterial adhesins MAM7, MshA1, and VpadF are known to promote cytotoxicity through recognition of specific host proteins (Krachler and Orth, 2011; Liu and Chen, 2015; O’Boyle et al, 2013). Our data suggest that sulfated host GAGs potentiate bacterial adhesion by promoting early stages of binding between partially redundant adhesins and host cells prior to recognition of specific targets.…”

Section: Discussionmentioning

confidence: 99%

CRISPR/Cas9 Screens Reveal Requirements for Host Cell Sulfation and Fucosylation in Bacterial Type III Secretion System-Mediated Cytotoxicity

Blondel

Park

Hubbard

et al. 2016

Cell Host & Microbe

View full text Add to dashboard Cite

SUMMARY Type III secretion systems (T3SSs) inject bacterial effector proteins into host cells and underlie the virulence of many Gram-negative pathogens. Studies have illuminated bacterial factors required for T3SS function, but the required host processes remain largely undefined. We coupled CRISPR/Cas9 genome editing technology with the cytotoxicity of two Vibrio parahaemolyticus T3SSs (T3SS1 and T3SS2) to identify human genome disruptions conferring resistance to T3SS-dependent cytotoxicity. We identity non-overlapping genes required for T3SS1- and T3SS2-mediated cytotoxicity. Genetic ablation of cell surface sulfation reduces bacterial adhesion and thereby alters the kinetics of T3SS1-mediated cytotoxicity. Cell surface fucosylation is required for T3SS2-dependent killing, and pharmacological or genetic inhibition of fucosylation prevents membrane insertion of the T3SS2 translocon complex. These findings reveal the importance of ubiquitous surface modifications for T3SS function, potentially explaining the broad tropism of V. parahaemolyticus, as well as highlight the utility of genome-wide CRISPR/Cas9 screens to discover processes underlying host-pathogen interactions.

show abstract

Section: Discussionmentioning

confidence: 99%

CRISPR/Cas9 Screens Reveal Requirements for Host Cell Sulfation and Fucosylation in Bacterial Type III Secretion System-Mediated Cytotoxicity

Blondel

Park

Hubbard

et al. 2016

Cell Host & Microbe

View full text Add to dashboard Cite

show abstract

“…Type IV pili bind to inert surfaces, as well as to bacterial and host cells; contact is established through pili retraction [37]. Disruption of Type IV pili is usually correlated with reduced adherence and virulence [38,39]. A V. parahaemolyticus strain lacking the MSHA pilus exhibited a more than twofold reduction in its adherence to Caco-2 (colonic epithelial) cells, as opposed to the wild-type strain.…”

Section: Msha Pilusmentioning

confidence: 99%

“…The loss in host cell adherence was correlated with a significant decrease in bacterial uptake by Caco-2 cells upon deletion of the mshA1 gene. MSHA pilus-mediated adhesion to epithelial cells was also required for V. parahaemolyticus-induced Caco-2 cell rounding, interleukin-8 (IL-8) secretion, and cytotoxicity, all of which are characteristic of a T3SS1 response, which requires efficient bacterial-host contact to achieve secretion of its components [39].…”

Section: Msha Pilusmentioning

confidence: 99%

Vibrio parahaemolyticus virulence determinants

Santos

Salomon

Krachler

et al. 2015

The Comprehensive Sourcebook of Bacterial Protein Toxins

View full text Add to dashboard Cite

“…In addition, genes encoding accessory colonization factors, such as mshA, gbpA, and acfABCD, have been identified in different V. cholerae strains, and it is possible that similar gene products contribute to AM-19226 colonization by coordinating functions early in infection, providing activities that can sustain robust colonization, or fine-tuning localization in the host niche (35). For example, while V. cholerae mshA expression is repressed during human infection, the V. parahaemolyticus MshA pilus apparently enables T3SS-mediated pathogenicity in vitro (36,37). In addition, GbpA contributes to the ability of O1 serogroup strains to successfully colonize mammalian host tissues and zooplankton, but substrate binding (chitin versus mucus) is specified by different domains within the modular structure of the protein (38,39).…”

Section: Fig 4 ⌬Vcsn2mentioning

confidence: 99%

Type Three Secretion System Island-Encoded Proteins Required for Colonization by Non-O1/Non-O139 Serogroup Vibrio cholerae

et al. 2015

View full text Add to dashboard Cite

Vibrio cholerae is a genetically diverse species, and pathogenic strains can encode different virulence factors that mediate colonization and secretory diarrhea. Although the toxin-coregulated pilus (TCP) is the primary colonization factor in epidemic-causing V. cholerae strains, other strains do not encode the TCP and instead promote colonization via the activity of a type 3 secretion system (T3SS). Using the infant mouse model and T3SS-positive O39 serogroup strain AM-19226, we sought to determine which of 12 previously identified, T3SS-translocated proteins (Vops) are important for host colonization. We constructed inframe deletions in each of the 12 loci in strain AM-19226 and identified five Vop deletion strains, including ⌬VopM, which were severely attenuated for colonization. Interestingly, a subset of deletion strains was also incompetent for effector protein transport. Our collective data therefore suggest that several translocated proteins may also function as components of the structural apparatus or translocation machinery and indicate that while VopM is critical for establishing an infection, the combined activities of other effectors may also contribute to the ability of T3SS-positive strains to colonize host epithelial cell surfaces. The toxin-coregulated pilus (TCP) is the major colonization factor encoded by all pathogenic O1 and O139 serogroup Vibrio cholerae strains, which cause epidemic cholera. In contrast, most clinically isolated non-O1/non-O139 serogroup strains do not encode TCP and thus must employ other mechanisms to effectively colonize the human intestinal epithelium and cause sporadic, cholera-like disease (1-3). Genome sequence analysis of a clinically isolated O39 serogroup strain, named AM-19226, identified a pathogenicity island on the large chromosome that encodes the structural proteins for a type 3 secretion system (T3SS) (4). T3SSs function as principal virulence mechanisms in many Gram-negative bacterial pathogens (e.g., Escherichia, Salmonella, Pseudomonas, Shigella, and Yersinia spp.), and in vivo studies using different animal models confirmed that the V. cholerae T3SS is essential for causing disease (5-7). In addition, numerous groups have identified T3SS-positive V. cholerae strains in laboratory collections, from patients, and from endemic environments, suggesting that a subset of non-O1/non-O139 serogroup strains depends on T3SS activity for virulence (1,3,4,(8)(9)(10).The V. cholerae T3SS is most closely related to the Vibrio parahaemolyticus T3SS2. T3SS2 is associated with pandemic V. parahaemolyticus strains, whereas T3SS1 is present in all strains (11). Comparison of the T3SS genomic islands in V. cholerae strain AM-19226 and V. parahaemolyticus strain RIMD2210633 reveals synteny within a conserved, central "core" region, flanked by 5= and 3= regions of greater coding diversity between clades and species (4, 10, 12-14). The core region encodes proteins that form the T3SS structural apparatus and is transcriptionally organized into four main operons in V. cholera...

show abstract

The MSHA pilus of Vibrio parahaemolyticus has lectin functionality and enables TTSS-mediated pathogenicity

Cited by 45 publications

References 43 publications

CRISPR/Cas9 Screens Reveal Requirements for Host Cell Sulfation and Fucosylation in Bacterial Type III Secretion System-Mediated Cytotoxicity

CRISPR/Cas9 Screens Reveal Requirements for Host Cell Sulfation and Fucosylation in Bacterial Type III Secretion System-Mediated Cytotoxicity

Vibrio parahaemolyticus virulence determinants

Type Three Secretion System Island-Encoded Proteins Required for Colonization by Non-O1/Non-O139 Serogroup Vibrio cholerae

Contact Info

Product

Resources

About