LfhA, a Novel Factor H-Binding Protein of
            <i>Leptospira interrogans</i>

Verma, Ashutosh; Hellwage, Jens; Artiushin, Sergey; Zipfel, Peter F.; Kraiczy, Peter; Timoney, John F.; Stevenson, Brian

doi:10.1128/iai.74.5.2659-2666.2006

Cited by 168 publications

(179 citation statements)

References 58 publications

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“…62 Leptospiral binding proteins to C4BP, factor H, and factor H-like have been identified in Leptospira. 17,18,46,[63][64][65][66] We report that Lsa23 is a novel C4BP and factor H binding protein of Leptospira, although with the ligand affinity for factor H binding protein seems to be low.…”

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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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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“…More recently, fH-binding proteins have been identified in Leptospira interrogans (31), West Nile virus (32), and Neisseria meningitidis (33). We have shown that N. gonorrhoeae evades complement killing by using its Por molecules to bind HufH (6).…”

mentioning

confidence: 94%

Human Factor H Interacts Selectively with Neisseria gonorrhoeae and Results in Species-Specific Complement Evasion

Ngampasutadol

Ram

Gulati

et al. 2008

The Journal of Immunology

116

143

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Complement forms a key arm of innate immune defenses against gonococcal infection. Sialylation of gonococcal lipo-oligosaccharide, or expression of porin 1A (Por1A) protein, enables Neisseria gonorrhoeae to bind the alternative pathway complement inhibitor, factor H (fH), and evade killing by human complement. Using recombinant fH fragment-murine Fc fusion proteins, we localized two N. gonorrhoeae Por1A-binding regions in fH: one in complement control protein domain 6, the other in complement control proteins 18–20. The latter is similar to that reported previously for sialylated Por1B gonococci. Upon incubation with human serum, Por1A and sialylated Por1B strains bound full-length human fH (HufH) and fH-related protein 1. In addition, Por1A strains bound fH-like protein 1 weakly. Only HufH, but not fH from other primates, bound directly to gonococci. Consistent with direct HufH binding, unsialylated Por1A gonococci resisted killing only by human complement, but not complement from other primates, rodents or lagomorphs; adding HufH to these heterologous sera restored serum resistance. Lipo-oligosaccharide sialylation of N. gonorrhoeae resulted in classical pathway regulation as evidenced by decreased C4 binding in human, chimpanzee, and rhesus serum but was accompanied by serum resistance only in human and chimpanzee serum. Direct-binding specificity of HufH only to gonococci that prevents serum killing is restricted to humans and may in part explain species-specific restriction of natural gonococcal infection. Our findings may help to improve animal models for gonorrhea while also having implications in the choice of complement sources to evaluate neisserial vaccine candidates.

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“…To escape complement, many pathogens use the deposition of complement inhibition molecules, such as factor H, on their membranes. Verma et al (6) described a Leptospira interrogans molecule that can bind to factor H (LfhA) avoiding complement activation. In addition, it was shown that human serum opsonization of pathogenic leptospires increased the adherence to neutrophils via the complement component C3 receptor (CR3) instead of K.A.…”

Section: Introductionmentioning

confidence: 99%

High levels of serum mannose-binding lectin are associated with the severity of clinical signs of leptospirosis

Miranda

Vasconcelos

Coelho

et al. 2009

Braz J Med Biol Res

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The clinical heterogeneity observed in leptospirosis may be associated with host factors or bacteria virulence. Human serum mannose-binding lectin (MBL) recognizes many pathogens, and low levels of this lectin are associated with susceptibility to infection. MBL is also implicated in the modulation of the inflammatory process. We determined the levels of serum MBL during leptospirosis infection. A double-antibody sandwich ELISA was used to detect the immunoreactive serum MBL. The ELISA plates were coated with monoclonal antibody to MBL and bound MBL or recombinant human MBL were detected by rabbit antihuman MBL serum. HRPO-conjugated goat anti-rabbit antibody was used for detection of the reaction. Two groups of patients seen at referral hospitals in Recife, PE, Brazil, were divided according to the year of infection, 2001 (N = 61) or 2002 (N = 57) and compared in terms of disease severity and levels of serum MBL. A group of healthy volunteers (N = 97) matched by age, gender, and ethnic background was used as control. Patients infected in 2001 had more severe outcomes than those infected in 2002, including jaundice, hemorrhage, respiratory alteration, and renal complication (P = 0.0009; chi-square test). The frequency of patients producing serum MBL >1000 ng/mL was higher in the 2001 group than in the 2002 and control groups (P < 0.01), suggesting an association of MBL level with disease severity. The involvement of MBL and genetic variation of the MBL2 gene should be further evaluated to establish the role of this lectin in the pathogenesis of leptospirosis.

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LfhA, a Novel Factor H-Binding Protein of Leptospira interrogans

Cited by 168 publications

References 58 publications

Characterization of Three Novel Adhesins of Leptospira interrogans

Characterization of Three Novel Adhesins of Leptospira interrogans

Human Factor H Interacts Selectively with Neisseria gonorrhoeae and Results in Species-Specific Complement Evasion

High levels of serum mannose-binding lectin are associated with the severity of clinical signs of leptospirosis

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