scholarly journals Characterization of Complement Factor H Binding to Yersinia enterocolitica Serotype O:3

2008 ◽  
Vol 76 (9) ◽  
pp. 4100-4109 ◽  
Author(s):  
Marta Biedzka-Sarek ◽  
Hanna Jarva ◽  
Heidi Hyytiäinen ◽  
Seppo Meri ◽  
Mikael Skurnik
Keyword(s):  
Yersinia Enterocolitica ◽  
Outer Core ◽  
Factor H ◽  
Negative Regulator ◽  
Complement Factor ◽  
Short Consensus Repeats ◽  
Serotype O ◽  
Complement Resistance ◽  
Number Of Bacteria

ABSTRACT A number of bacteria bind factor H (FH), the negative regulator of the alternative complement pathway, to avoid complement-mediated killing. Here we show that a gram-negative enteric pathogen, Yersinia enterocolitica serotype O:3, uses two virulence-related outer membrane (OM) proteins to bind FH. With Y. enterocolitica O:3 mutant strains displaying different combinations of surface factors relevant to complement resistance, we demonstrated that the major receptor for FH is the OM protein YadA. Another OM protein, Ail, also contributes to FH binding provided that it is not blocked by distal parts of the lipopolysaccharide (i.e., the O antigen and the outer core hexasaccharide). Importantly, we demonstrated that surface-bound FH was functional; both YadA- and Ail-bound FH displayed cofactor activity for factor I-mediated cleavage of C3b. With truncated recombinant FH constructs, we located the binding site of Ail specifically to short consensus repeats 6 and 7 of FH, while YadA showed a novel type of FH-binding pattern and appears to bind FH throughout the entire FH molecule. We thus conclude that Y. enterocolitica, via YadA and Ail, recruits functionally active FH to its surface. FH binding appears to be an important mechanism of the complement resistance of this pathogen.

scholarly journals Functional Mapping of YadA- and Ail-Mediated Binding of Human Factor H to Yersinia enterocolitica Serotype O:3

2008 ◽  
Vol 76 (11) ◽  
pp. 5016-5027 ◽  
Author(s):  
Marta Biedzka-Sarek ◽  
Saara Salmenlinna ◽  
Markus Gruber ◽  
Andrei N. Lupas ◽  
Seppo Meri ◽  
...  
Keyword(s):  
Yersinia Enterocolitica ◽  
Alternative Pathway ◽  
Outer Membrane Proteins ◽  
Factor H ◽  
Complement Alternative Pathway ◽  
Human Host ◽  
Serotype O ◽  
Complement Resistance ◽  
Sense And Respond ◽  
Active Complement

ABSTRACT Yersinia enterocolitica is an enteric pathogen that exploits diverse means to survive in the human host. Upon Y. enterocolitica entry into the human host, bacteria sense and respond to variety of signals, one of which is the temperature. Temperature in particular has a profound impact on Y. enterocolitica gene expression, as most of its virulence factors are expressed exclusively at 37°C. These include two outer membrane proteins, YadA and Ail, that function as adhesins and complement resistance (CR) factors. Both YadA and Ail bind the functionally active complement alternative pathway regulator factor H (FH). In this study, we characterized regions on both proteins involved in CR and the interaction with FH. Twenty-eight mutants having short (7 to 41 amino acids) internal deletions within the neck and stalk of YadA and two complement-sensitive site-directed Ail mutants were constructed to map the CR and FH binding regions of YadA and Ail. Functional analysis of the YadA mutants revealed that the stalk of YadA is required for both CR and FH binding and that FH appears to target several conformational and discontinuous sites of the YadA stalk. On the other hand, the complement-sensitive Ail mutants were not affected in FH binding. Our results also suggested that Ail- and YadA-mediated CR does not depend solely on FH binding.

scholarly journals Characterization of Binding Properties of Individual Functional Sites of Human Complement Factor H

2020 ◽  
Vol 11 ◽  
Author(s):  
Aftabul Haque ◽  
Claudio Cortes ◽  
M. Nurul Alam ◽  
Maladi Sreedhar ◽  
Viviana P. Ferreira ◽  
...  
Keyword(s):  
Factor H ◽  
Complement Factor H ◽  
Complement Factor ◽  
Human Complement ◽  
Binding Properties ◽  
Functional Sites

scholarly journals The Human Complement Regulator Factor H Binds Pneumococcal Surface Protein PspC via Short Consensus Repeats 13 to 15

2002 ◽  
Vol 70 (10) ◽  
pp. 5604-5611 ◽  
Author(s):  
Thomas G. Duthy ◽  
Rebecca J. Ormsby ◽  
Eleni Giannakis ◽  
A. David Ogunniyi ◽  
Uwe H. Stroeher ◽  
...  
Keyword(s):  
Alternative Pathway ◽  
Regulatory System ◽  
Surface Protein ◽  
Fluid Phase ◽  
Direct Consequence ◽  
Factor H ◽  
Negative Regulator ◽  
Short Consensus Repeats ◽  
High Concentrations ◽  
Complement Regulator

ABSTRACT The innate ability of Streptococcus pneumoniae to resist complement activation and complement-mediated phagocytosis may be a direct consequence of the ability of the bacteria to bind components of the complement regulatory system. One such component, factor H (fH), is a crucial fluid-phase negative regulator of the alternative pathway of complement and is utilized by a number of pathogenic organisms to resist complement attack. The pneumococcal surface protein C (PspC [also known as CbpA] and SpsA) has been shown to bind fH, although the exact binding site within one or more of the 20 short consensus repeats (SCRs) of the molecule is not known. The purpose of the current study was to map specific SCRs on fH responsible for this binding. Initial experiments utilizing type 2 pneumococcal strain D39 and its isogenic PspC-negative derivative (D39/pspC mutant) showed that fH binding was PspC dependent. A purified recombinant protein derivative of PspC that lacked the proline-rich region (PspCΔPro) had a reduced binding efficiency for fH, thereby directly showing the importance of this region for the fH interaction. We have specifically shown by inhibition experiments that SCRs responsible for heparin and C3b binding of fH are not involved in binding PspC and the interaction between fH and PspC is largely hydrophobic, since no inhibition was observed in the presence of high concentrations of NaCl. Construction of SCR proteins encompassing the whole fH molecule showed that SCRs 8 to 15 (SCR 8-15) mediated binding to PspC. Further localization experiments revealed that SCR 13 and SCR 15 were required for full binding, although partial binding was retained when either SCR was removed.

scholarly journals Yersinia enterocolitica : Biochemical, Serological, and Gas-Liquid Chromatographic Characterization of Rhamnose-, Raffinose-, Melibiose-, and Citrate-Utilizing Strains

1977 ◽  
Vol 6 (5) ◽  
pp. 461-468
Author(s):  
Brent Chester ◽  
Guenther Stotzky ◽  
Edward J. Bottone ◽  
Moises S. Malowany ◽  
Jona Allerhand
Keyword(s):  
Yersinia Enterocolitica ◽  
Yersinia Pseudotuberculosis ◽  
Gas Liquid Chromatography ◽  
Susceptibility Data ◽  
Serotype O ◽  
Chromatographic Characterization ◽  
O 15 ◽  
Liquid Chromatographic ◽  
Lactic Acids

Thirteen atypical Yersinia enterocolitica isolates, all fermenting rhamnose, raffinose, and melibiose and utilizing sodium citrate within 24 to 48 h at 22°C ( Y.e.rh +), were examined biochemically-serologically, and by gas-liquid chromatography. These data, as well as cultural, biochemical, and antibiotic susceptibility data gathered from two previous studies involving (i) these same atypical Y.e.rh + isolates, (ii) Y. enterocolitica serotypes O:1 through O:15 (rhamnose, raffinose, and citrate negative [ Y.e.rh −]), (iii) Y. enterocolitica serotype O:16 (rhamnose positive but raffinose and citrate negative), and (iv) Yersinia pseudotuberculosis serogroups I through V were statistically compared. Both preand postabsorption agglutination studies demonstrated the serological distinctiveness of Y.e.rh + from Y.e.rh − and Y. pseudotuberculosis . At the same time, three immunological groups among the 13 Y.e.rh + strains were seen; 8 corresponded to Y. enterocolitica serotype O:17; 1 to Y. enterocolitica serotype O:16; and the remaining four were nontypable in antisera against known Y. enterocolitica antigen types. Each of the three Yersinia groups tested chromatographically produced acetic and lactic acids. Both Y.e.rh − and Y.e.rh + formed propionic acid, but only Y.e.rh + produced detectable amounts of succinic acid. Based on 49 variables, statistical analysis of the three Yersinia groups studied placed each of the Y.e.rh + strains in a homogeneous group separate from both Y.e.rh − and Y. pseudotuberculosis . These data, coupled with deoxyribonucleic acid homology studies of Brenner and co-workers (D. J. Brenner, A. G. Steigerwalt, D. F. Falcao, R. E. Weaver, and G. R. Fanning, Int. J. Syst. Bacteriol. 26 :180-194, 1976), support the distinctiveness of Y.e.rh + from typical Y. enterocolitica and Y. pseudotuberculosis .

Characterization of binding properties of individual functional sites of complement factor H

2018 ◽  
Vol 102 ◽  
pp. 148
Author(s):  
Viviana Ferreira ◽  
Aftabul Haque ◽  
Claudio Cortes ◽  
M. Nurul Alam ◽  
Maladi Sreedhar ◽  
...  
Keyword(s):  
Factor H ◽  
Complement Factor H ◽  
Complement Factor ◽  
Binding Properties ◽  
Functional Sites

scholarly journals Characterization of Neisseria meningitidis Isolates That Do Not Express the Virulence Factor and Vaccine Antigen Factor H Binding Protein

2011 ◽  
Vol 18 (6) ◽  
pp. 1002-1014 ◽  
Author(s):  
Jay Lucidarme ◽  
Lionel Tan ◽  
Rachel M. Exley ◽  
Jamie Findlow ◽  
Ray Borrow ◽  
...  
Keyword(s):  
Neisseria Meningitidis ◽  
Binding Protein ◽  
Factor H ◽  
Negative Regulator ◽  
Vaccine Antigen ◽  
Natural Immunity ◽  
Content Type ◽  
Reading Frame ◽  
Flanking Sequences

ABSTRACTNeisseria meningitidisremains a leading cause of bacterial sepsis and meningitis. Complement is a key component of natural immunity against this important human pathogen, which has evolved multiple mechanisms to evade complement-mediated lysis. One approach adopted by the meningococcus is to recruit a human negative regulator of the complement system, factor H (fH), to its surface via a lipoprotein, factor H binding protein (fHbp). Additionally, fHbp is a key antigen in vaccines currently being evaluated in clinical trials. Here we characterize strains ofN. meningitidisfrom several distinct clonal complexes which do not express fHbp; all strains were recovered from patients with disseminated meningococcal disease. We demonstrate that these strains have either a frameshift mutation in thefHbpopen reading frame or have entirely lostfHbpand some flanking sequences. No fH binding was detected to other ligands among thefHbp-negative strains. The implications of these findings for meningococcal pathogenesis and prevention are discussed.

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