Leptospira Immunoglobulin-Like Protein B Interacts with the 20th Exon of Human Tropoelastin Contributing to Leptospiral Adhesion to Human Lung Cells

Hsieh, Ching-Lin; Tseng, Andrew; He, Hongxuan; Kuo, C.J.; Wang, Xuannian; Chang, Yung-Fu

doi:10.3389/fcimb.2017.00163

Cited by 11 publications

(6 citation statements)

References 41 publications

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“…Saprophytic strain L. biflexa serovar Patoc (Patoc 1) showed binding only to the endothelial HULEC5a cell line ( Figure 1 B), possibly due to some sticker properties. In general, we confirmed that the bacterial adhesion results corroborate with those in the literature [ 11 , 19 ].…”

Section: Resultssupporting

confidence: 92%

“…In other investigations, leptospiral proteins, including LigA, LigB, OmpL1, rLIC11574, rLIC13411, rLIC12976 and rLIC10831, were assayed in monolayers of mammalian cells, but the main focus of these studies was the binding of proteins to glycosaminoglycans (GAGs) and ECM. Of the proteins studied, only OmpL1 showed significant binding to both mammalian cell lines tested [ 7 , 13 , 18 , 19 , 20 , 21 ].…”

Section: Introductionmentioning

confidence: 99%

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Host Cell Binding Mediated by Leptospira interrogans Adhesins

Takahashi

Teixeira

Nascimento

2022

IJMS

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Leptospirosis is a neglected infectious disease with global impact on both humans and animals. The increase in urban development without sanitation planning is one of the main reasons for the disease spreading. The symptoms are similar to those of flu-like diseases, such as dengue, yellow fever, and malaria, which can result in a misleading clinical diagnosis. The characterization of host–pathogen interactions is important in the development of new vaccines, treatments, and diagnostics. However, the pathogenesis of leptospirosis is not well understood, and many gaps remain to be addressed. Here, we aimed to determine if Leptospira strains, virulent, culture-attenuated, and saprophytic, and the major outer membrane proteins OmpL37, OmpL1, LipL21, LipL41, and LipL46 are able to adhere to different endothelial, epithelial and fibroblast cell lines in vitro. We showed that virulent leptospires robustly bind to all cells compared to the culture-attenuated and saprophytic lines. The recombinant proteins exhibited certain adhesion, but only OmpL1 and LipL41 were able to bind to several cell lines, either in monolayer or in cell suspension. Blocking OmpL1 with polyclonal antibodies caused a decrease in bacterial binding to cells, contrasting with an increase observed when anti-LipL41 antibodies were used. The adhesion of OmpL1 to HMEC-1 and EA.hy926 was inhibited when cells were pre-incubated with collagen IV, suggesting that both compete for the same cell receptor. We present here for the first time the interaction of five leptospiral outer membrane proteins with several cell lines, and we conclude that LipL41 and OmpL1 may have an impact on leptospiral adhesion to mammalian cells and may mediate the colonization process in leptospiral pathogenesis.

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Section: Resultssupporting

confidence: 92%

Section: Introductionmentioning

confidence: 99%

Host Cell Binding Mediated by Leptospira interrogans Adhesins

Takahashi

Teixeira

Nascimento

2022

IJMS

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“…Studies presented here and elsewhere [91] demonstrate for the first time that both PerRA and PerRB are required for full transcription of the virulence-related genes ligA and ligB . These pathogen-specific surface lipoproteins have been studied extensively for their contributions to host-pathogen interactions [176, 177], virulence [178] and potential use as vaccinogens [179–181]. Using a TALE-based transcriptional knockdown approach, Pappas and Picardeau [178] reported that both Ligs are required for virulence in hamsters.…”

Section: Discussionmentioning

confidence: 99%

The FUR-like regulators PerRA and PerRB integrate a complex regulatory network that promotes mammalian host-adaptation and virulence ofLeptospira interrogans

Zavala-Alvarado

Bettin

et al. 2020

Preprint

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Leptospira interrogans , the causative agent of most cases of human leptospirosis, must respond to myriad environmental signals during its free-living and pathogenic lifestyles. Previously, we compared L. interrogans cultivated in vitro and in vivo using a dialysis membrane chamber (DMC) peritoneal implant model. From these studies emerged 160 genes that were differentially regulated in response to host signals, including perRA , one of two Peroxide stress response (PerR)-like regulators encoded by L. interrogans . Zavala-Alvarado et al . recently demonstrated that leptospires lacking both PerRA and PerRB are avirulent in hamsters. Herein, we establish that PerRA and PerRB also are required for renal colonization in C3H/HeJ mice. The finding that loss of virulence was observed only with the perRA/B double mutant suggests that these regulators serve redundant or overlapping functions in vivo . Our finding that the perRA / B double mutant survives at wild-type levels in DMCs is noteworthy as it demonstrates that the loss of virulence is not due to a metabolic lesion ( i.e. , metal starvation) but instead reflects dysregulation of virulence-related gene products. Comparative RNA-seq analyses of perRA , perRB and perRA/B mutants cultivated within DMCs identified 106 genes that are dysregulated only in the double mutant, including ligA, ligB and lvrA/B sensory histidine kinases. Decreased expression of LigA and LigB in the perRA / B mutant was not due to loss of LvrAB signal transduction. The majority of genes in the PerRA and PerRB DMC regulons was differentially expressed only in vivo , highlighting the importance of host-specific signals for regulating gene expression in L. interrogans . Importantly, the PerRA, PerRB and PerRA/B DMC regulons each contain multiple genes related to environmental sensing and/or transcriptional regulation. Collectively, our data suggest that PerRA and PerRB are part of a complex signaling network required by L. interrogans for adaptation to and survival within the host.

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“…The terminal repeats of the proteins LigA and LigB, which interacted with the gelatin binding domain of fibronectin, were able to bind to MDCK cells and inhibited the ligation of L. interrogans serovar Pomona to the monolayers ( Lin et al., 2010 ). Also, LigB and a mutant of L. biflexa expressing LigA showed binding to human embryonic lung cells and these interactions were blocked in the presence of human tropoelastin up to 68% and 61%, respectively ( Hsieh et al., 2017 ).…”

Section: Cell Interactions and Adhesionmentioning

confidence: 99%

A Review on Host-Leptospira Interactions: What We Know and Future Expectations

Daroz

Fernandes

Cavenague

et al. 2021

Front. Cell. Infect. Microbiol.

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Leptospirosis is a widespread zoonosis caused by pathogenic Leptospira spp. It is considered a neglected infectious disease of human and veterinary concern. Our group has been investigating proteins annotated as hypothetical, predicted to be located on the leptospiral surface. Because of their location, these proteins may have the ability to interact with various host components, which could allow establishment of the infection. These proteins act as adherence factors by binding to host receptor molecules, such as the extracellular matrix (ECM) components laminin and glycosaminoglycans to help bacterial colonization. Leptospira also interacts with the host fibrinolytic system, which has been demonstrated to be a powerful tool for invasion mechanisms. The interaction with fibrinogen and thrombin has been shown to reduce fibrin clot formation. Additionally, the degradation of coagulation cascade components by secreted proteases or by acquired surface plasmin could also play a role in reducing clot formation, hence facilitating dissemination during infection. Interaction with host complement system regulators also plays a role in helping bacteria to evade the immune system, facilitating invasion. Interaction of Leptospira to cell receptors, such as cadherins, can contribute to investigate molecules that participate in virulence. To achieve a better understanding of the host-pathogen interaction, leptospiral mutagenesis tools have been developed and explored. This work presents several proteins that mediate binding to components of the ECM, plasma, components of the complement system and cells, to gather research achievements that can be helpful in better understanding the mechanisms of leptospiral-host interactions and discuss genetic manipulation for Leptospira spp. aimed at protein function validation.

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Leptospira Immunoglobulin-Like Protein B Interacts with the 20th Exon of Human Tropoelastin Contributing to Leptospiral Adhesion to Human Lung Cells

Cited by 11 publications

References 41 publications

Host Cell Binding Mediated by Leptospira interrogans Adhesins

Host Cell Binding Mediated by Leptospira interrogans Adhesins

The FUR-like regulators PerRA and PerRB integrate a complex regulatory network that promotes mammalian host-adaptation and virulence ofLeptospira interrogans

A Review on Host-Leptospira Interactions: What We Know and Future Expectations

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