Leptospira spp.: Novel insights into host–pathogen interactions

Fernandes, Luis G. V.; Siqueira, Gabriela H.; Teixeira, Aline F.; Silva, Lucas P.; Figueredo, Jupciana M.; Cosate, Maria Raquel Venturim; Vieira, Mônica L.; Nascimento, Ana L. T. O.

doi:10.1016/j.vetimm.2015.12.004

Cited by 47 publications

(41 citation statements)

References 86 publications

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“…It is known that pathogenic leptospires are capable of binding to structural components of the ECM, such as collagen, laminin, fibronectin and cell-surface receptors, such as cadherins [52,53]. Several leptospiral proteins expressed in E. coli as Histag recombinant proteins have been characterized in vitro as putative adhesins that could mediate the binding of the bacteria to the host components [10,54]. The involvement of His-tag on the binding was excluded because many of these recombinant proteins did not interact with the ECM components tested [46,55].…”

Section: Discussionmentioning

confidence: 99%

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%

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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“…This is true as well for Leptospira spp. (Fernandes et al, 2016;Murray, 2015;Picardeau, 2017). However, even with their basic similarities in structure-each of the crystalized leptospiral LRR proteins forms the classic solenoid structure (Miras et al, 2015)-there may also be clearly defined roles for the different members of the Leptospira LRR protein family.…”

Section: Lic10831 Also Binds Human Ve-cadherinmentioning

confidence: 99%

An extracellular Leptospira interrogans leucine‐rich repeat protein binds human E‐ and VE‐cadherins

Eshghi

Gaultney

England

et al. 2018

Cellular Microbiology

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Pathogenic Leptospira bacteria are the causative agents of leptospirosis, a zoonotic disease affecting animals and humans worldwide. These pathogenic species have the ability to rapidly cross host tissue barriers by a yet unknown mechanism. A comparative analysis of pathogens and saprophytes revealed a higher abundance of genes encoding proteins with leucine-rich repeat (LRR) domains in the genomes of pathogens. In other bacterial pathogens, proteins with LRR domains have been shown to be involved in mediating host cell attachment and invasion. One protein from the pathogenic species Leptospira interrogans, LIC10831, has been previously analysed via X-ray crystallography, with findings suggesting it may be an important bacterial adhesin. Herein we show that LIC10831 elicits an antibody response in infected animals, is actively secreted by the bacterium, and binds human E- and VE-cadherins. These results provide biochemical and cellular evidences of LRR protein-mediated host-pathogen interactions and identify a new multireceptor binding protein from this infectious Leptospira species.

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“…Após a adesão, as leptospiras devem superar barreiras físicas impostas pelas células e tecidos até atingir a corrente sanguínea. Nosso grupo demonstrou pela primeira vez a habilidade da leptospira patogênica de capturar o plasminogênio (PLG) circulante por meio de suas OMPs e, na presença de ativadores do plasminogênio do próprio hospedeiro, ser convertido em plasmina (PLA), uma serino-protease de amplo espectro que confere à bactéria um revestimento proteolítico capaz de degradar laminina e fibronectina, e deste modo contribui para a invasão destes microrganismos (Vieira et al, 2009;Vieira et al, 2013;Fernandes et al, 2016). Já foi demonstrado que a atividade proteolítica da leptospira proveniente da ligação à plasmina também é capaz de degradar a molécula C3b do sistema complemento, imunoglobulinas e fibrinogênio (Fg) (Vieira et al, 2011;Oliveira et al, 2013).…”

Section: Mecanismos De Patogenicidade E Fatores De Virulência Da Leptunclassified

“…Um outro mecanismo utilizado pela leptospira para invadir é por meio da captura do Fg circulante e como consequência ocorre a diminuição da formação de coágulos de fibrina, aumento de hemorragias e maior facilidade de disseminação da bactéria (Oliveira et al, 2013;Fernandes et al, 2016).…”

Section: Mecanismos De Patogenicidade E Fatores De Virulência Da Leptunclassified

Avaliação do papel funcional de duas proteínas de >i<Leptospira interrogans>/i< no processo de adesão do patógeno ao hospedeiro

Kochi¹

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Aos meus pais, Choei e Ivete, principais responsáveis pela minha educação e formação, dedico este trabalho. AGRADECIMENTOS À Deus, pelo simples fato de viver e poder desfrutar de experiências magníficas ao longo da vida. Aos antepassados, que se sacrificaram deixando a terra natal para encontrar aqui uma nova esperança de vida. Aos meus pais, Ivete e Choei (in memoriam), pelo amor incondicional, pelas broncas merecidas e por todos os esforços para me educar e me moldar em um homem de caráter. À minha irmã, Renata, minha melhor amiga e companheira de todas as horas, para sempre. A todos os meus familiares, pelo apoio incondicional e por exemplificar perfeitamente o significado de "família". À Ana Cristina (Tininha), minha namorada, amiga e companheira. Agradeço por todo amor e paciência, por sempre estar ao meu lado nos momentos decisivos, pelos momentos maravilhosos que já passamos e pelos momentos que ainda vivenciaremos. Aos irmãos que a vida me deu, Lucas, Cássio, André, Patrick, Bruno e Gustavo, pelos momentos de diversão e risadas... os bons momentos da vida! Aos grandes amigos Rafael, Danilo, José, Bruno, Wiliam, Henrique e Leonardo, parceiros desde a escola, obrigado pelos incentivos e horas de jogatinas. GG WP. À minha orientadora, Dra. Ana Lucia Tabet Oller do Nascimento, pela oportunidade dada em ingressar em um grupo de pesquisa de excelência no Instituto Butantan, pelo aprendizado diário e desenvolvimento da mentalidade crítica, que com certeza ajudaram muito para meu crescimento como cientista. Ao Dr. Luis Guilherme Virgílio Fernandes, pela amizade e companheirismo diário, dentro e fora do laboratório, por toda a paciência e dedicação ao ensinar. Com certeza é mais um irmão que a vida me proporcionou.

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Leptospira spp.: Novel insights into host–pathogen interactions

Cited by 47 publications

References 86 publications

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

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

An extracellular Leptospira interrogans leucine‐rich repeat protein binds human E‐ and VE‐cadherins

Avaliação do papel funcional de duas proteínas de >i<Leptospira interrogans>/i< no processo de adesão do patógeno ao hospedeiro

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