Leptospiral Endostatin-Like Protein A Is a Bacterial Cell Surface Receptor for Human Plasminogen

Verma, Ashutosh; Brissette, Catherine A.; Bowman, Amy; Shah, Samir T.; Zipfel, Peter F.; Stevenson, Brian

doi:10.1128/iai.01282-09

Cited by 81 publications

(93 citation statements)

References 48 publications

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“…Of note, the functionally related but genetically heterologous complement regulator-acquiring surface proteins CspA, CspZ, ErpP, ErpC, and ErpA all bind plasminogen in addition to binding various host-derived complement regulators (28,29,(63)(64)(65)(66). Other pathogenic microorganisms have proteins that also bind both plasminogen and complement regulators, such as factor H, factor H-like protein 1, factor H-related protein-1, or C4b-binding protein (23,26,27,(67)(68)(69). Notably, although BBA70 is orthologous to the borrelial factor H-and plasminogen-binding CspA protein, BBA70 is unable to bind any tested complement regulators (52).…”

Section: Discussionmentioning

confidence: 99%

BBA70 of Borrelia burgdorferi Is a Novel Plasminogen-binding Protein

Koenigs

Hammerschmidt

Jutras

et al. 2013

Journal of Biological Chemistry

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Background: Recruitment of plasminogen is important for efficient dissemination of Borrelia burgdorferi. Results: BBA70 of B. burgdorferi binds plasminogen, and following activation, bound plasmin can cleave fibrinogen and inactivate the key complement components C3b and C5. Conclusion: BBA70 is a potent plasminogen-binding protein.Significance: Investigation suggests that binding of plasminogen may aid in pathogen dissemination and inhibit bacteriolytic effects of the host complement system.

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Section: Discussionmentioning

confidence: 99%

BBA70 of Borrelia burgdorferi Is a Novel Plasminogen-binding Protein

Koenigs

Hammerschmidt

Jutras

et al. 2013

Journal of Biological Chemistry

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“…by our group. 19 Verma and others 55 have shown that the protein LenA of L. interrogans is a surface receptor for human PLG. Furthermore, several PLG-binding proteins of Leptospira have been identified.…”

Section: Discussionmentioning

confidence: 99%

Characterization of Three Novel Adhesins of Leptospira interrogans

Siqueira¹,

Atzingen²,

Alves³

et al. 2013

The American Society of Tropical Medicine and Hygiene

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Abstract. We report cloning, expression, purification, and characterization of three predicted leptospiral membrane proteins (LIC11360, LIC11009, and LIC11975). In silico analysis and proteinase K accessibility data suggest that these proteins might be surface exposed. We show that proteins encoded by LIC11360, LIC11009 and LIC11975 genes interact with laminin in a dose-dependent and saturable manner. The proteins are referred to as leptospiral surface adhesions 23, 26, and 36 (Lsa23, Lsa26, and Lsa36), respectively. These proteins also bind plasminogen and generate active plasmin. Attachment of Lsa23 and Lsa36 to fibronectin occurs through the involvement of the 30-kDa and 70-kDa heparin-binding domains of the ligand. Dose-dependent, specific-binding of Lsa23 to the complement regulator C4BP and to a lesser extent, to factor H, suggests that this protein may interfere with the complement cascade pathways. Leptospira spp. may use these interactions as possible mechanisms during the establishment of infection.

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“…P la s m a f ib r o n e c t in C e ll u la r f ib r o n e c t in E la s t in G e la t in B S A F e t u in serum serum recombinant proteins Fernandes et al, 2012;Mendes et al, 2011;Oliveira et al, 2011;Souza et al, 2012;Verma et al, 2010;Vieira et al, 2010b), a microplate was coated with Lsa44 or Lsa45, incubated with PLG, a urokinase (uPA)-type PLG activator and a PLAspecific chromogenic substrate (see Methods). The PLG bound to the proteins could be converted into PLA, as demonstrated indirectly by the specific proteolytic activity (Fig.…”

Section: Pla Generation From Bound Plgmentioning

confidence: 99%

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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Leptospiral Endostatin-Like Protein A Is a Bacterial Cell Surface Receptor for Human Plasminogen

Cited by 81 publications

References 48 publications

BBA70 of Borrelia burgdorferi Is a Novel Plasminogen-binding Protein

BBA70 of Borrelia burgdorferi Is a Novel Plasminogen-binding Protein

Characterization of Three Novel Adhesins of Leptospira interrogans

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

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