Characterization of Three Novel Adhesins of Leptospira interrogans

Siqueira, Gabriela H.; Atzingen, Marina V.; Alves, Ivy J.; Morais, Zenáide Maria de; Vasconcellos, Sílvio Arruda; Nascimento, Ana L. T. O.

doi:10.4269/ajtmh.13-0205

Cited by 43 publications

(60 citation statements)

References 66 publications

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“…This includes purified extracellular matrix laminin and fibronectin molecules and serum components, such as the complement regulators FH and C4BP, and the zymogen PLG. Moreover, Lsa23 is recognized by antibodies present in positive leptospirosis patients and is probably expressed during infection (Siqueira et al, 2013). We thus decided to further characterize these interactions with the aim of gathering information on the role of Lsa23 in immune evasion strategies of Leptospira.…”

Section: Introductionmentioning

confidence: 99%

Leptospira interrogans Lsa23 protein recruits plasminogen, factor H and C4BP from normal human serum and mediates C3b and C4b degradation

et al. 2016

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It has been reported that pathogenic Leptospira are resistant to normal human serum (NHS) due to their ability to evade the complement immune system by interacting with factor H (FH) and C4b-binding protein (C4BP) regulators. Moreover, plasmin generation on the leptospiral surface diminishes C3b and IgG deposition, decreasing opsonophagocytosis by immune competent cells. We have previously reported that Lsa23 (LIC11360) is a multipurpose protein capable of binding purified extracellular matrix molecules, FH, C4BP and plasminogen (PLG)/plasmin in the presence of PLG activators. In this work, we provide further evidence that Lsa23 is located at the bacterial surface by using immunofluorescence microscopy. We show that Lsa23 has the ability to acquire FH, C4BP and PLG from NHS, and use these interactions to evade innate immunity. The binding with the complement regulators FH and C4BP preserves factor I (FI) activity, leading to C3b and C4b degradation products, respectively. C3b and C4b alpha-chain cleavage was also observed when Lsa23 bound to PLG generating plasmin, an effect blocked by the protease inhibitor aprotinin. Lsa23 also inhibited lytic activity by NHS mediated by both classical and alternative complement pathways. Thus, Lsa23 has the ability to block both pathways of the complement system, and may help pathogenic Leptospira to escape complement-mediated clearance in human hosts. Indeed, NHS treated with Lsa23 confers a partial serum resistance phenotype to Leptospira biflexa, whereas blocking this protein with anti-Lsa23 renders pathogenic L. interrogans more susceptible to complement-mediated killing. Thus, Lsa23 is a multifunctional protein involved in many pathways, featuring C4b cleavage by plasmin, knowledge that may help in the development of preventive approaches to intervene with human complement escape by this versatile pathogen.

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Section: Introductionmentioning

confidence: 99%

Leptospira interrogans Lsa23 protein recruits plasminogen, factor H and C4BP from normal human serum and mediates C3b and C4b degradation

et al. 2016

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“…Lsa27, Lsa20, Lsa25, Lsa33 e Lsa26 são proteínas de leptospiras identificadas quanto à sua capacidade de interação com laminina (DOMINGOS et al, 2012;LONGHI et al, 2009;MENDES et al, 2011;SIQUEIRA et al, 2013), enquanto outras proteínas, como LipL53 e Lsa21, foram descritas com base na sua ligação à laminina, colágeno IV, fibronectina celular e plasmática. Além disso, a expressão dessas proteínas parece ser restrita a linhagens virulenta e, ainda, Lsa21 parece ser regulada por condição osmótica e temperatura, sugerindo o seu potencial para patogênese da bactéria (ATZINGEN et al, 2008;OLIVEIRA et al, 2010).…”

Section: Mecanismos De Patogenicidadeunclassified

“…Além disso, foi demonstrado que a atividade de plasmina pode conferir alguma vantagem relacionada à evasão imune, visto que plasmina gerada na superfície das leptospiras foi capaz de interferir na deposição de IgG e C3b na superfície da bactéria, reduzindo o processo de opsonização (VIEIRA et al, 2011). Diante da importância desse sistema, diversas proteínas de membrana de leptospiras têm sido avaliadas quanto à interação com PLG, sendo que uma quantidade bastante expressiva de proteínas foi identificada como receptores de PLG (DOMINGOS et al, 2012;FERNANDES et al, 2014;FERNANDES et al, 2012;MENDES et al, 2011;OLIVEIRA et al, 2011;SIQUEIRA et al, 2013;SIQUEIRA et al, 2016;SOUZA et al, 2012;VIEIRA et al, 2010a;.…”

Section: Mecanismos De Patogenicidadeunclassified

“…Outras proteínas com propriedades multifuncionais também foram identificadas pelo nosso grupo, como ligantes de C4BP (DOMINGOS et al, 2012;SIQUEIRA et al, 2013;SIQUEIRA et al, 2016;SOUZA et al, 2012). …”

Section: Mecanismos De Patogenicidadeunclassified

“…Em seguida, a interação destas proteínas com PLG e fibronectina plasmática foi avaliado por ELISA. SIQUEIRA et al, 2013).…”

Section: Efeito Das Proteínas Lsa46 E Lsa77 Desnaturadas Na Ligação Aunclassified

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Avaliação e caracterização de candidatos vacinais voltados para o controle da leptospirose.

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Evaluation of binding activities of a putative lipoprotein LIC_13355 of Leptospira spp.

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et al. 2024

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Pathogenic Leptospira is the etiological cause of the zoonotic life‐threatening infection called leptospirosis. The disease is spread worldwide with higher risk in tropical regions. Although leptospirosis represents a burden to the health of humans and animals, the pathogenic mechanisms of Leptospira infection are yet to be clarified. Leptospirosis infection is multifactorial, involving functionally redundant proteins with the capability to invade, disseminate, and escape the host's immune response. In this work, we describe a putative lipoprotein encoded by the gene LIC_13355, genome annotated as hypothetical of unknown function. The coding sequence is conserved among pathogenic Leptospira spp. with high percentage of coverage and identity. The recombinant protein, rLIC_13355, was expressed in Escherichia coli host system in its insoluble form. The circular dichroism spectrum of the refolded protein showed it containing a mixture of secondary structures. rLIC_13355 interacts with extracellular matrix (ECM) component laminin and binds plasminogen (PLG), generating plasmin (PLA), thus possibly participating during the adhesion and dissemination processes. The rLIC_13355 has the ability to interact with Ea.hy926 and HMEC‐1 endothelial cells either in monolayer or suspension. The binding of rLIC_13355 with monolayer cells is dose‐dependent on protein concentration. Taken together, our data suggest that this is presumably an adhesion lipoprotein that may play diverse roles in host–Leptospira interactions by mediating the interaction with host components and with endothelial cell.

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Characterization of Three Novel Adhesins of Leptospira interrogans

Cited by 43 publications

References 66 publications

Leptospira interrogans Lsa23 protein recruits plasminogen, factor H and C4BP from normal human serum and mediates C3b and C4b degradation

Leptospira interrogans Lsa23 protein recruits plasminogen, factor H and C4BP from normal human serum and mediates C3b and C4b degradation

Avaliação e caracterização de candidatos vacinais voltados para o controle da leptospirose.

Evaluation of binding activities of a putative lipoprotein LIC_13355 of Leptospira spp.

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