Lsa21, a novel leptospiral protein binding adhesive matrix molecules and present during human infection

Atzingen, Marina V.; Barbosa, Angela Silva; Brito, Thales de; Vasconcellos, Sílvio Arruda; Morais, Zenáide Maria de; Lima, Dirce M. C.; Abreu, Patrícia Antônia Estima; Nascimento, Ana L. T. O.

doi:10.1186/1471-2180-8-70

Cited by 108 publications

(135 citation statements)

References 55 publications

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“…Protein attachment to individual macromolecules of ECM (all from Sigma) and serum components (EMD Chemicals) was analysed according to a previously reported protocol (Atzingen et al, 2008). Briefly, ELISA plates (Costar High Binding; Corning) were coated with 1 mg each component or the negative controls BSA, gelatin and fetuin in 100 ml PBS for 3 h at 37 uC, and then blocked overnight at 4 uC.…”

Section: Methodsmentioning

confidence: 99%

“…Indeed, we have reported that pathogenic leptospires are capable of binding ECM macromolecules (Barbosa et al, 2006). Thus far, several proteins of Leptospira have been assigned as possible mediators for ECM attachment (Atzingen et al, 2008(Atzingen et al, , 2009Barbosa et al, 2006;Carvalho et al, 2009;Choy et al, 2007;Domingos et al, 2012;Fernandes et al, 2012;Hoke et al, 2008; Mendes et al, 2011;Oliveira et al, 2010Oliveira et al, , 2011Pinne et al, 2010;Souza et al, 2012;Stevenson et al, 2007;Vieira et al, 2010a). After adherence, pathogens have to overcome host tissue barriers to reach the blood circulation and target organs.…”

Section: Introductionmentioning

confidence: 99%

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Functional and immunological evaluation of two novel proteins of Leptospira spp.

et al. 2014

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This work shows the production and characterization of two novel putative lipoproteins encoded by the genes LIC10645 and LIC10731 identified in the genome sequences of Leptospira interrogans. In silico conservation analysis indicated that the proteins are well conserved among pathogenic leptospiral serovars and species. Recombinant proteins were obtained in Escherichia coli BL21(DE3) Star pLysS strain, purified by metal-affinity chromatography, and used for characterization and immunological evaluations. Recombinant proteins were capable of eliciting a combination of humoral and cellular immune responses in animal models, and could be recognized by antibodies present in human serum samples. The recombinant proteins Lsa44 and Lsa45 were able to bind laminin, and were named Lsa44 and Lsa45 for leptospiral surface adhesins of 44 and 45 kDa, respectively. The attachment to laminin was dose-responsive with K D values of 108.21 and 250.38 nM for Lsa44 and Lsa45, respectively. Moreover, these proteins interact with plasminogen (PLG) with K D values of 53.56 and 36.80 nM, respectively. PLG bound to the recombinant proteins could be converted to plasmin (PLA) in the presence of an activator. Cellular localization assays suggested that the Lsa44 and Lsa45 were surface-exposed. These are versatile proteins capable of interacting with laminin and PLG/PLA, and hence could mediate bacterial adhesion and contribute to tissue penetration. INTRODUCTIONLeptospirosis is a zoonosis of global importance caused by pathogenic bacterial species of the genus Leptospira (Bharti et al., 2003;Faine et al., 1999). In urban environments, rodents are the main host reservoirs of leptospires, shedding live bacteria through their urine (Ko et al., 1999;Vinetz et al., 1996). Humans are infected via contact with urine of wild or domestic animal carriers, either directly or indirectly through contaminated water or soil (Adler & de la Peña Moctezuma, 2010). The disease presents a broad spectrum of symptoms, including fever, vomiting, headache, diarrhoea, and abdominal and generalized muscle pain. Due to these flu-like signs, leptospirosis remains under-diagnosed. Progression to multiorgan system complications, known as Weil's syndrome, occurs in 5-15 % of cases, with mortality rates of 5-40 % (Faine et al., 1999;Ko et al., 1999;Levett, 2001; Plank & Dean, 2000).Currently available commercial vaccines are based on inactivated whole-cell or membrane preparations of pathogenic leptospires, named bacterins. They confer protective responses mostly through the induction of antibodies against LPS antigens (Adler & de la Peña Moctezuma, 2010; de la Peña-Moctezuma et al., 1999). Nevertheless, these vaccines do not induce long-term protection against infection and do not provide cross-protective immunity against leptospiral serovars not included in the vaccine preparation (Adler & de la Peña Moctezuma, 2010). Due to the large number of serovars (Bharti et al., 2003), the search for conserved and protective antigens is being pursued (Koizumi & Watanabe, 2005...

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Functional and immunological evaluation of two novel proteins of Leptospira spp.

et al. 2014

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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). Outras proteínas que apresentam capacidade de ligação a vários componentes da ECM já foram identificadas VIEIRA et al, 2014).…”

Section: Mecanismos De Patogenicidadeunclassified

“…Para isso, laminina, fibronectina celular, elastina, colágeno tipo I, colágeno tipo IV e as proteínas controles BSA e fetuína foram imobilizados em placas de microdiluição e a ligação das proteínas recombinantes foi avaliada por ELISA, após o uso dos anticorpos policlonais obtidos contra cada proteína recombinante. Várias proteínas de leptospiras com propriedades de ligação específica a laminina e a outros componentes da ECM foram identificadas pelo nosso grupo (ATZINGEN et al, 2008;ATZINGEN et al, 2009;BARBOSA et al, 2006;DOMINGOS et al, 2015;DOMINGOS et al, 2012;FERNANDES et al, 2014;FERNANDES et al, 2012;LONGHI et al, 2009;MENDES et al, 2011;OLIVEIRA et al, 2011;OLIVEIRA et al, 2010; __________________________________________________________Resultados e Discussão 113 2013; SOUZA et al, 2012;VIEIRA et al, 2010b). Outros grupos também identificaram proteínas com capacidade de adesão (CARVALHO et al, 2009;CHOY et al, 2007;HAUK et al, 2008;HOKE et al, 2008;LIN et al, 2009;STEVENSON et al, 2007).…”

Section: Adesão Das Proteínas Recombinantes a Componentes Da Matriz Eunclassified

“…(Figura 36). Nossos achados foram semelhantes aos resultados obtidos por Fernandes e colaboradores (2012) com a proteína OmpL1, mas, difere dos dados encontrados para a maioria dos outros ligantes de laminina (ATZINGEN et al, 2008;BARBOSA et al, 2006;DOMINGOS et al, 2012;OLIVEIRA et al, 2010). De qualquer forma, esses resultados indicam que nem todas as adesinas interagem com laminina na mesma região.…”

Section: Importância Dos Resíduos De Carboidratos Na Interação De Lamunclassified

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

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Lsa21, a novel leptospiral protein binding adhesive matrix molecules and present during human infection

Cited by 108 publications

References 55 publications

Functional and immunological evaluation of two novel proteins of Leptospira spp.

Functional and immunological evaluation of two novel proteins of Leptospira spp.

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

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