scholarly journals Analysis of the Virulence of an Atypical EnteropathogenicEscherichia coliStrainIn VitroandIn Vivoand the Influence of Type Three Secretion System

2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Suely C. F. Sampaio ◽  
Fabiana C. Moreira ◽  
Ana M. A. Liberatore ◽  
Mônica A. M. Vieira ◽  
Terezinha Knobl ◽  
...  
Keyword(s):  
Secretion System ◽  
Mesenteric Lymph Nodes ◽  
Invasive Potential ◽  
Virulence Potential ◽  
Type Three Secretion System ◽  
Isogenic Mutant Strain ◽  
Type Three Secretion

Atypical enteropathogenicEscherichia coli(aEPEC) inject various effectors into intestinal cells through a type three secretion system (T3SS), causing attaching and effacing (A/E) lesions. We investigated the role of T3SS in the ability of the aEPEC 1711-4 strain to interact with enterocytesin vitro(Caco-2 cells) andin vivo(rabbit ileal loops) and to translocate the rat intestinal mucosain vivo. A T3SS isogenic mutant strain was constructed, which showed marked reduction in the ability to associate and invade but not to persist inside Caco-2 cells. After rabbit infection, only aEPEC 1711-4 was detected inside enterocytes at 8 and 24 hours pointing to a T3SS-dependent invasive potentialin vivo. In contrast to aEPEC 1711-4, the T3SS-deficient strain no longer produced A/E lesions or induced macrophage infiltration. We also demonstrated that the ability of aEPEC 1711-4 to translocate through mesenteric lymph nodes to spleen and liver in a rat model depends on a functional T3SS, since a decreased number of T3SS mutant bacteria were recovered from extraintestinal sites. These findings indicate that the full virulence potential of aEPEC 1711-4 depends on a functional T3SS, which contributes to efficient adhesion/invasionin vitroandin vivoand to bacterial translocation to extraintestinal sites.

scholarly journals Laboratory Adaptation of Bordetella pertussis Is Associated with the Loss of Type Three Secretion System Functionality

2011 ◽  
Vol 79 (9) ◽  
pp. 3677-3682 ◽  
Author(s):  
M. E. Gaillard ◽  
D. Bottero ◽  
C. E. Castuma ◽  
L. A. Basile ◽  
D. Hozbor
Keyword(s):  
Bordetella Pertussis ◽  
Growth Conditions ◽  
Secretion System ◽  
Clinical Isolates ◽  
Content Type ◽  
Type Three Secretion System ◽  
Associated Proteins ◽  
Type Three Secretion

ABSTRACTAlthoughBordetella pertussiscontains and transcribes loci encoding type III secretion system (TTSS) homologues, expression of TTSS-associated proteins has been reported only for non-laboratory-adapted Irish clinical isolates. Here we confirm such a result for clinical isolates obtained from patients treated in Argentinean hospitals. Moreover, we demonstrate that the expression of TTSS-associated proteins is independent both of the year in which the isolate was obtained and of the types of polymorphic alleles for other virulence factors but is dependent on environmental growth conditions. Interestingly, we observed that TTSS-associated protein expression is lost after successivein vitropassages but becomes operative again when bacteria come into contact with the host. Thisin vivoactivation of TTSS expression was observed not only for clinical isolates previously adapted to the laboratory after successivein vitropassages but also for vaccine strains that did not express the systemin vitro. The reversibility of TTSS expression, demonstrated by its switching off-on when the bacterium comes into contact with the host, appears to be an adaptive response of this pathogen.

scholarly journals Small Molecule Inhibitor of Type Three Secretion System Belonging to a Class 2,4-disubstituted-4H-[1,3,4]-thiadiazine-5-ones Improves Survival and Decreases Bacterial Loads in an AirwayPseudomonas aeruginosaInfection in Mice

2018 ◽  
Vol 2018 ◽  
pp. 1-13 ◽  
Author(s):  
Anna B. Sheremet ◽  
Naylia A. Zigangirova ◽  
Egor S. Zayakin ◽  
Sergei I. Luyksaar ◽  
Lydia N. Kapotina ◽  
...  
Keyword(s):  
Small Molecule ◽  
Small Molecule Inhibitor ◽  
Secretion System ◽  
Resistant Bacteria ◽  
Lung Pathology ◽  
Antibiotic Resistant ◽  
Molecule Inhibitor ◽  
Type Three Secretion System ◽  
Type Three Secretion

Pseudomonas aeruginosais a cause of high mortality in burn, immunocompromised, and surgery patients. High incidence of antibiotic resistance in this pathogen makes the existent therapy inefficient. Type three secretion system (T3SS) is a leading virulence system ofP. aeruginosathat actively suppresses host resistance and enhances the severity of infection. Innovative therapeutic strategies aiming at inhibition of type three secretion system ofP. aeruginosaare highly attractive, as they may reduce the severity of clinical manifestations and improve antibacterial immune responses. They may also represent an attractive therapy for antibiotic-resistant bacteria. Recently our laboratory developed a new small molecule inhibitor belonging to a class 2,4-disubstituted-4H-[1,3,4]-thiadiazine-5-ones, Fluorothiazinon (FT), that effectively suppressed T3SS in chlamydia and salmonellain vitroandin vivo.In this study, we evaluate the activity of FT towards antibiotic-resistant clinical isolates ofP. aeruginosaexpressing T3SS effectors ExoU and ExoS in an airway infection model. We found that FT reduced mortality and bacterial loads and decrease lung pathology and systemic inflammation. In addition, we show that FT inhibits the secretion of ExoT and ExoY, reduced bacteria cytotoxicity, and increased bacteria internalizationin vitro. Overall, FT shows a strong potential as an antibacterial therapy of antibiotic-resistantP. aeruginosainfection.

scholarly journals Role for the Burkholderia pseudomallei Type Three Secretion System Cluster 1bpscNGene in Virulence

2011 ◽  
Vol 79 (9) ◽  
pp. 3659-3664 ◽  
Author(s):  
Tanya D'Cruze ◽  
Lan Gong ◽  
Puthayalai Treerat ◽  
Georg Ramm ◽  
John D. Boyce ◽  
...  
Keyword(s):  
Mammalian Cells ◽  
Burkholderia Pseudomallei ◽  
Gene Clusters ◽  
Secretion System ◽  
Host Cells ◽  
Infection Model ◽  
Content Type ◽  
Type Three Secretion System ◽  
Type Three Secretion

ABSTRACTBurkholderia pseudomallei, the causal agent of melioidosis, employs a number of virulence factors during its infection of mammalian cells. One such factor is the type three secretion system (TTSS), which is proposed to mediate the transport and secretion of bacterial effector molecules directly into host cells. TheB. pseudomalleigenome contains three TTSS gene clusters (designated TTSS1, TTSS2, and TTSS3). Previous research has indicated that neither TTSS1 nor TTSS2 is involved inB. pseudomalleivirulence in a hamster infection model. We have characterized aB. pseudomalleimutant lacking expression of the predicted TTSS1 ATPase encoded bybpscN. This mutant was significantly attenuated for virulence in a respiratory melioidosis mouse model of infection. In addition, analysesin vitroshowed diminished survival and replication in RAW264.7 cells and an increased level of colocalization with the autophagy marker protein LC3 but an unhindered ability to escape from phagosomes. Taken together, these data provide evidence that the TTSS1bpscNgene product plays an important role in the intracellular survival ofB. pseudomalleiand the pathogenesis of murine infection.

scholarly journals vttRA and vttRB Encode ToxR Family Proteins That Mediate Bile-Induced Expression of Type Three Secretion System Genes in a Non-O1/Non-O139 Vibrio cholerae Strain

2010 ◽  
Vol 78 (6) ◽  
pp. 2554-2570 ◽  
Author(s):  
Ashfaqul Alam ◽  
Vincent Tam ◽  
Elaine Hamilton ◽  
Michelle Dziejman
Keyword(s):  
Gene Expression ◽  
Vibrio Cholerae ◽  
Secretion System ◽  
Regulatory Proteins ◽  
Cholerae Strain ◽  
Type Three Secretion System ◽  
Genes Encoding ◽  
Intergenic Regions ◽  
Type Three Secretion

ABSTRACT Strain AM-19226 is a pathogenic non-O1/non-O139 serogroup Vibrio cholerae strain that does not encode the toxin-coregulated pilus or cholera toxin but instead causes disease using a type three secretion system (T3SS). Two genes within the T3SS pathogenicity island, herein named vttR A (locus tag A33_1664) and vttR B (locus tag A33_1675), are predicted to encode proteins that show similarity to the transcriptional regulator ToxR, which is found in all strains of V. cholerae. Strains with a deletion of vttR A or vttR B showed attenuated colonization in vivo, indicating that the T3SS-encoded regulatory proteins play a role in virulence. lacZ transcriptional reporter fusions to intergenic regions upstream of genes encoding the T3SS structural components identified growth in the presence of bile as a condition that modulates gene expression. Under this condition, VttRA and VttRB were necessary for maximal gene expression. In contrast, growth in bile did not substantially alter the expression of a reporter fusion to the vopF gene, which encodes an effector protein. Increased vttR B reporter fusion activity was observed in a ΔvttR B strain background, suggesting that VttRB may regulate its own expression. The collective results are consistent with the hypothesis that T3SS-encoded regulatory proteins are essential for pathogenesis and control the expression of selected T3SS genes.

scholarly journals The invasive pathogen Yersinia pestis disrupts host blood vasculature to spread and provoke hemorrhages

2021 ◽  
Vol 15 (10) ◽  
pp. e0009832
Author(s):  
Guillain Mikaty ◽  
Héloïse Coullon ◽  
Laurence Fiette ◽  
Javier Pizarro-Cerdá ◽  
Elisabeth Carniel
Keyword(s):  
Yersinia Pestis ◽  
Vascular System ◽  
Type Three Secretion System ◽  
Invasive Capacity ◽  
Host Blood ◽  
Work Supports ◽  
Type Three Secretion ◽  
Draining Lymph Nodes

Yersinia pestis is a powerful pathogen with a rare invasive capacity. After a flea bite, the plague bacillus can reach the bloodstream in a matter of days giving way to invade the whole organism reaching all organs and provoking disseminated hemorrhages. However, the mechanisms used by this bacterium to cross and disrupt the endothelial vascular barrier remain poorly understood. In this study, an innovative model of in vivo infection was used to focus on the interaction between Y. pestis and its host vascular system. In the draining lymph nodes and in secondary organs, bacteria provoked the porosity and disruption of blood vessels. An in vitro model of endothelial barrier showed a role in this phenotype for the pYV/pCD1 plasmid that carries a Type Three Secretion System. This work supports that the pYV/pCD1 plasmid is responsible for the powerful tissue invasiveness capacity of the plague bacillus and the hemorrhagic features of plague.

scholarly journals The Role of Coupled Positive Feedback in the Expression of the SPI1 Type Three Secretion System in Salmonella

2010 ◽  
Vol 6 (7) ◽  
pp. e1001025 ◽  
Author(s):  
Supreet Saini ◽  
Jeremy R. Ellermeier ◽  
James M. Slauch ◽  
Christopher V. Rao
Keyword(s):  
Positive Feedback ◽  
Secretion System ◽  
Type Three Secretion System ◽  
Type Three Secretion

scholarly journals DksA coordinates bile-mediated regulation of virulence-associated phenotypes in type three secretion system-positive Vibrio cholerae

Microbiology ◽  
2020 ◽  
Author(s):  
Madeline K. Sofia ◽  
Michelle Dziejman
Keyword(s):  
Gene Expression ◽  
Vibrio Cholerae ◽  
Type Species ◽  
Regulatory Networks ◽  
Stringent Response ◽  
Secretion System ◽  
Content Type ◽  
Type Three Secretion System ◽  
Type Three Secretion

In order to cause disease, pathogenic strains of Vibrio cholerae rely on intricate regulatory networks to orchestrate the transition between their native aquatic environment and the human host. For example, bacteria in a nutrient-starved environment undergo a metabolic shift called the stringent response, which is mediated by the alarmone ppGpp and an RNA-polymerase binding transcriptional factor, DksA. In O1 serogroup strains of V. cholerae, which use the toxin co-regulated pilus (TCP) and cholera toxin (CT) as primary virulence factors, DksA was reported to have additional functions as a mediator of virulence gene expression. However, little is known about the regulatory networks coordinating virulence phenotypes in pathogenic strains that use TCP/CT-independent virulence mechanisms. We therefore investigated whether functions of DksA outside of the stringent response are conserved in type three secretion system (T3SS)-positive V. cholerae . In using the T3SS-positive clinically isolated O39 serogroup strain AM-19226, we observed an increase in dksA expression in the presence of bile at 37 °C. However, DksA was not required for wild-type levels of T3SS structural gene expression, or for colonization in vivo. Rather, data indicate that DksA positively regulates the expression of master regulators in the motility hierarchy. Interestingly, the ΔdksA strain forms a less robust biofilm than the WT parent strain at both 30 and 37 °C. We also found that DksA regulates the expression of hapR, encoding a major regulator of biofilm formation and protease expression. Athough DksA does not appear to modulate T3SS virulence factor expression, its activity is integrated into existing regulatory networks governing virulence-related phenotypes. Strain variations therefore may take advantage of conserved ancestral proteins to expand regulons responding to in vivo signals and thus coordinate multiple phenotypes important for infection.

Sign in / Sign up

Export Citation Format

Share Document