Unknown

Dataset Information

0

VE-cadherin cleavage by LasB protease from Pseudomonas aeruginosa facilitates type III secretion system toxicity in endothelial cells.


ABSTRACT: Infection of the vascular system by Pseudomonas aeruginosa (Pa) occurs during bacterial dissemination in the body or in blood-borne infections. Type 3 secretion system (T3SS) toxins from Pa induce a massive retraction when injected into endothelial cells. Here, we addressed the role of type 2 secretion system (T2SS) effectors in this process. Mutants with an inactive T2SS were much less effective than wild-type strains at inducing cell retraction. Furthermore, secretomes from wild-types were sufficient to trigger cell-cell junction opening when applied to cells, while T2SS-inactivated mutants had minimal activity. Intoxication was associated with decreased levels of vascular endothelial (VE)-cadherin, a homophilic adhesive protein located at endothelial cell-cell junctions. During the process, the protein was cleaved in the middle of its extracellular domain (positions 335 and 349). VE-cadherin attrition was T3SS-independent but T2SS-dependent. Interestingly, the epithelial (E)-cadherin was unaffected by T2SS effectors, indicating that this mechanism is specific to endothelial cells. We showed that one of the T2SS effectors, the protease LasB, directly affected VE-cadherin proteolysis, hence promoting cell-cell junction disruption. Furthermore, mouse infection with Pa to induce acute pneumonia lead to significant decreases in lung VE-cadherin levels, whereas the decrease was minimal with T2SS-inactivated or LasB-deleted mutant strains. We conclude that the T2SS plays a pivotal role during Pa infection of the vascular system by breaching the endothelial barrier, and propose a model in which the T2SS and the T3SS cooperate to intoxicate endothelial cells.

SUBMITTER: Golovkine G 

PROVIDER: S-EPMC3953407 | biostudies-literature | 2014 Mar

REPOSITORIES: biostudies-literature

altmetric image

Publications

VE-cadherin cleavage by LasB protease from Pseudomonas aeruginosa facilitates type III secretion system toxicity in endothelial cells.

Golovkine Guillaume G   Faudry Eric E   Bouillot Stéphanie S   Voulhoux Romé R   Attrée Ina I   Huber Philippe P  

PLoS pathogens 20140313 3


Infection of the vascular system by Pseudomonas aeruginosa (Pa) occurs during bacterial dissemination in the body or in blood-borne infections. Type 3 secretion system (T3SS) toxins from Pa induce a massive retraction when injected into endothelial cells. Here, we addressed the role of type 2 secretion system (T2SS) effectors in this process. Mutants with an inactive T2SS were much less effective than wild-type strains at inducing cell retraction. Furthermore, secretomes from wild-types were suf  ...[more]

Similar Datasets

| S-EPMC7511813 | biostudies-literature
| S-EPMC177776 | biostudies-other
| S-EPMC3037957 | biostudies-literature
| S-EPMC4693985 | biostudies-literature
| S-EPMC10770215 | biostudies-literature
| S-EPMC4404142 | biostudies-literature
| S-EPMC6907878 | biostudies-literature
| S-EPMC8234315 | biostudies-literature
| S-EPMC2754073 | biostudies-literature
| S-EPMC4868686 | biostudies-literature