Multifunctional and Redundant Roles of Leptospira interrogans Proteins in Bacterial-Adhesion and fibrin clotting inhibition

Pereira, Priscila Romero Mazzini; Fernandes, Luis G. V.; Souza, Gisele Oliveira de; Vasconcellos, Sílvio Arruda; Heinemann, Marcos Bryan; Romero, Eliete Caló; Nascimento, Ana L. T. O.

doi:10.1016/j.ijmm.2017.05.006

Cited by 23 publications

(39 citation statements)

References 67 publications

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“…Both recombinant proteins were characterized as novel E-cadherin (epithelial) ligands. The involvement of His-tag in mediating these interactions was ruled out since several recombinant proteins do not react with E-cadherin [14]. Recombinant LIC11711 exhibited a saturable dose-dependent binding to E-cadherin with a higher affinity than the previously described Lsa16 [14], and recombinant rLIC12587 also interacted in dose-dependent manner, but without reaching a saturation point.…”

Section: Discussionmentioning

confidence: 99%

“…The involvement of His-tag in mediating these interactions was ruled out since several recombinant proteins do not react with E-cadherin [14]. Recombinant LIC11711 exhibited a saturable dose-dependent binding to E-cadherin with a higher affinity than the previously described Lsa16 [14], and recombinant rLIC12587 also interacted in dose-dependent manner, but without reaching a saturation point. The K D for rLIC11711 and E-cadherin (3.82 ± 0.21 μM) is of the same order of magnitude when compared with rLIC10831 and the same component (K D 2.3 ± 0.3 μM) [56].…”

Section: Discussionmentioning

confidence: 99%

“…Wells were washed three times with PBS and incubated with 100 μL of HRP-conjugated antimouse IgG (1:5,000). The reactions were carried on, as previously described [14]. For statistical analysis, complete system for LIC11711 or LIC12587 was compared with LipL31 in each group by Student's t-test.…”

Section: Immunoblotting Assaymentioning

confidence: 99%

“…It is known that the process of initial leptospiral adhesion to biomolecules present in the cells that make up the epithelial tissue is a fundamental step for the success of the bacterial host invasion and colonization. In this aspect, the interaction with several extracellular matrix components (ECM) and to surface cellreceptors has already been investigated for leptospires by our group [9][10][11][12][13][14]. Another mechanism employed by pathogenic leptospires is the binding to circulating host plasma components.…”

Section: Introductionmentioning

confidence: 99%

“…Interaction of Leptospira to fibrinogen (Fg) leading to a partial inhibition of fibrin clotting formation through Fg/thrombincatalyzed reaction may help the bacterial dissemination [18]. Several proteins have the capacity to binding Fg but only in a few cases this interaction leads to fibrin clot inhibition [14,19].…”

Section: Introductionmentioning

confidence: 99%

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The interaction of two novel putative proteins of Leptospira interrogans with E-cadherin, plasminogen and complement components with potential role in bacterial infection

et al. 2019

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Leptospirosis is a worldwide zoonosis caused by pathogenic species of Leptospira. Leptospires are able to adhere to exposed extracellular matrix in injured tissues and, once in the bloodstream, can survive the attack of the immune system and spread to colonize target organs. In this work, we report that two novel putative proteins, coded by the genes LIC11711 and LIC12587 of L. interrogans serovar Copenhageni are conserved among pathogenic strains, and probably exposed in the bacterial surface. Soluble recombinant proteins were expressed in Escherichia coli, purified and characterized. Both recombinant proteins bound to laminin and E-cadherin, suggesting an initial adhesion function in host epithelial cells. The recombinant protein LIC11711 (rLIC11711) was able to capture plasminogen (PLG) from normal human serum and convert to enzymatically active plasmin (PLA), in the presence of PLG activator. rLIC12587 (recombinant protein LIC12587) displayed a dose dependent and saturable interaction with components C7, C8, and C9 of the complement system, reducing the bactericidal effect of the complement. Binding to C9 may have consequences such as C9 polymerization inhibition, interfering with the membrane attack complex formation. Blocking LIC11711 and LIC12587 on bacterial cells by the respective antiserum reduced leptospiral cell viability when exposed to normal human serum (NHS). Both recombinant proteins could be recognized by serum samples of confirmed leptospirosis, but not of unrelated diseases, suggesting that the native proteins are immunogenic and expressed during leptospirosis. Taken together, our data suggest that these proteins may have a role in leptospiral pathogenesis, participating in immune evasion strategies.

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Section: Discussionmentioning

confidence: 99%