Lepstospira interrogans shotgun phage display identified LigB as a heparin-binding protein

Ching, Ana Tung Ching; Fávaro, Regiane Degan; Lima, Swiany Silveira; Chaves, A.; Lima, Marcelo A.; Nader, Helena B.; Abreu, Patrícia Antônia Estima; Ho, Paulo Lee

doi:10.1016/j.bbrc.2012.09.137

Cited by 19 publications

(14 citation statements)

References 46 publications

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“…In a study on central nervous system infections, it was shown that HBP levels in the Cerebrospinal fluid in patients with acute bacterial meningitis increased significantly compared with other central nervous system infected patients [10]. HBP levels also increased significantly in inflammatory diseases caused by Leishmania chagasi, influenza (H1N1) virus and Leptospira interrogans [23,24,25]. In our study, HBP levels were significantly higher in patients with acute appendicitis compared with the control group.…”

Section: Discussionsupporting

confidence: 51%

Prognostic importance of plasma heparin binding protein in the diagnosis of acute appendicitis

Temiz¹

2019

Ann Clin Anal Med

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Aim: In recent years, it has been found that plasma levels of Heparin Binding Protein (HBP) are elevated in systemic inflammatory conditions. In this study, we aimed to demonstrate the diagnostic value of HBP in patients with acute appendicitis (AA). Material and Method: Sixty patients with acute appendicitis and 27 healthy subjects were included in the study. Plasma HBP levels were measured in the patient groups and control groups and the results were compared. Results: The average HBP level in the 60 patients with acute appendicitis (AA) was 9.63 ± 3.64 ng/ml, while the average HBP value of the healthy group was 7.65 ± 2.52 ng/ml. When the groups were compared, the HBP serum levels were significantly lower (p = 0.02) in the healthy control group. The area under the curve (AUC) was 0.785 in the ROC curve for diagnosis of acute appendicitis using HBP. Discussion: This study has significance as the first study to investigate the HBP level in patients with acute appendicitis, and HBP may be a potential new marker for the diagnosis of acute appendicitis.

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Section: Discussionsupporting

confidence: 51%

Prognostic importance of plasma heparin binding protein in the diagnosis of acute appendicitis

Temiz¹

2019

Ann Clin Anal Med

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“…With the limitations in the available genetic tools in Leptospira spp., phage display represents an alternative but powerful tool to identify Leptospira proteins with cell-binding activities, as well as the specific portions of the proteins with adhesin activities. This approach has also been employed in identifying Leptospira proteins that bind to ECM components [63] . Our experimental strategy eliminated adhesins that might bind to host molecules that might be deposited as extracellular matrix, or remain cell-associated.…”

Section: Discussionmentioning

confidence: 99%

“…Those appearing in bold were prioritized for further characterization. * Known L. interrogans adhesin [20] , [22] , [24] , [28] , [30] – [31] , [63] . a Inserted L. interrogans DNA in opposite orientation of the gene.…”

Section: Supporting Informationmentioning

confidence: 99%

Identification of Cell-Binding Adhesins of Leptospira interrogans

et al. 2014

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Leptospirosis is a globally distributed bacterial infectious disease caused by pathogenic members of the genus Leptospira. Infection can lead to illness ranging from mild and non-specific to severe, with jaundice, kidney and liver dysfunction, and widespread endothelial damage. The adhesion of pathogenic Leptospira species (spp.), the causative agent of leptospirosis, to host tissue components is necessary for infection and pathogenesis. While it is well-established that extracellular matrix (ECM) components play a role in the interaction of the pathogen with host molecules, we have shown that pathogenic Leptospira interrogans binds to host cells more efficiently than to ECM components. Using in vitro phage display to select for phage clones that bind to EA.hy926 endothelial cells, we identified the putative lipoproteins LIC10508 and LIC13411, and the conserved hypothetical proteins LIC12341 and LIC11574, as candidate L. interrogans sv. Copenhageni st. Fiocruz L1–130 adhesins. Recombinant LIC11574, but not its L. biflexa homologue LBF1629, exhibited dose-dependent binding to both endothelial and epithelial cells. In addition, LIC11574 and LIC13411 bind to VE-cadherin, an endothelial cell receptor for L. interrogans. Extraction of bacteria with the non-ionic detergent Triton X-114 resulted in partitioning of the candidate adhesins to the detergent fraction, a likely indication that these proteins are outer membrane localized. All candidate adhesins were recognized by sera obtained from leptospirosis patients but not by sera from healthy individuals as assessed by western blot. This work has identified bacterial adhesins that are potentially involved in L. interrogans infection of the mammalian host, and through cadherin binding, may contribute to dissemination and vascular damage. Our findings may be of value in leptospirosis control and prevention, with the bacterial adhesins potentially serving as targets for development of diagnostics, therapeutics, and vaccines.

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“…We then investigated if the above phenomenon could be a result of heparin binding directly to LigA and LigB. According to Ching and colleagues [ 35 ], recombinant LigBC binds to heparin, and this interaction may help L . interrogans to invade host cells.…”

Section: Resultsmentioning

confidence: 99%

Fine Mapping of the Interaction between C4b-Binding Protein and Outer Membrane Proteins LigA and LigB of Pathogenic Leptospira interrogans

et al. 2015

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The complement system consists of more than 40 proteins that participate in the inflammatory response and in pathogen killing. Complement inhibitors are necessary to avoid the excessive consumption and activation of this system on host cells. Leptospirosis is a worldwide zoonosis caused by spirochetes from the genus Leptospira. Pathogenic leptospires are able to escape from complement activation by binding to host complement inhibitors Factor H [FH] and C4b-binding protein (C4BP) while non-pathogenic leptospires are rapidly killed in the presence of fresh serum. In this study, we demonstrate that complement control protein domains (CCP) 7 and 8 of C4BP α-chain interact with the outer membrane proteins LcpA, LigA and LigB from the pathogenic leptospire L. interrogans. The interaction between C4BP and LcpA, LigA and LigB is sensitive to ionic strength and inhibited by heparin. We fine mapped the LigA and LigB domains involved in its binding to C4BP and heparin and found that both interactions are mediated through the bacterial immunoglobulin-like (Big) domains 7 and 8 (LigA7-8 and LigB7-8) of both LigA and LigB and also through LigB9-10. Therefore, C4BP and heparin may share the same binding sites on Lig proteins.

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Lepstospira interrogans shotgun phage display identified LigB as a heparin-binding protein

Cited by 19 publications

References 46 publications

Prognostic importance of plasma heparin binding protein in the diagnosis of acute appendicitis

Prognostic importance of plasma heparin binding protein in the diagnosis of acute appendicitis

Identification of Cell-Binding Adhesins of Leptospira interrogans

Fine Mapping of the Interaction between C4b-Binding Protein and Outer Membrane Proteins LigA and LigB of Pathogenic Leptospira interrogans

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