Human C4b-binding protein selectively interacts with<i>Neisseria gonorrhoeae</i>and results in species-specific infection

Ngampasutadol, Jutamas; Ram, Sanjay; Blom, Anna M.; Jarva, Hanna; Jerse, Ann E.; Lien, Egil; Goguen, Jon D.; Gulati, Sunita; Rice, Peter A.

doi:10.1073/pnas.0506471102

Cited by 84 publications

(99 citation statements)

References 51 publications

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“…Comparative studies of another member of the Ail family, Rck of S. typhimurium, may suggest that the mode of OmpX action is through inhibition of C9 polymerization and formation of the mature membrane attack complex (MAC) on the bacterial surface (Heffernan et al, 1992b). It has also been reported that Y. pestis binds the complement regulatory protein C4bp as observed by Ngampasutadol et al (2005). Whether Y. pestis OmpX is directly involved in these latter two processes is currently being examined.…”

Section: Discussionmentioning

confidence: 99%

Phenotypic characterization of OmpX, an Ail homologue of Yersinia pestis KIM

et al. 2007

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The goal of this study was to characterize the Yersinia pestis KIM OmpX protein. Yersinia spp. provide a model for studying several virulence processes including attachment to, and internalization by, host cells. For Yersinia enterocolitica and Yersinia pseudotuberculosis, Ail, YadA and Inv, have been implicated in these processes. In Y. pestis, YadA and Inv are inactivated. Genomic analysis of two Y. pestis strains revealed four loci with sequence homology to Ail. One of these genes, designated y1324 in the Y. pestis KIM database, encodes a protein designated OmpX. The mature protein has a predicted molecular mass of 17.47 kDa, shares approximately 70 % sequence identity with Y. enterocolitica Ail, and has an identical homologue, designated Ail, in the Y. pestis CO92 database. The present study compared the Y. pestis KIM6 + parental strain with a mutant derivative having an engineered disruption of the OmpX structural gene. The parental strain (and a merodiploid control strain) expressed OmpX at 28 and 37 6C, and the protein was detectable throughout all phases of growth. OmpX was required for efficient adherence to, and internalization by, cultured HEp-2 cell monolayers and conferred resistance to the bactericidal effect of human serum. Deletion of ompX resulted in a significantly reduced autoaggregation phenotype and loss of pellicle formation in vitro. These results suggest that Y. pestis OmpX shares functional homology with Y. enterocolitica Ail in adherence, internalization into epithelial cells and serum resistance.

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Section: Discussionmentioning

confidence: 99%

Phenotypic characterization of OmpX, an Ail homologue of Yersinia pestis KIM

et al. 2007

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“…Western blotting was performed as described previously (39). To detect direct bacterial binding of HufH, FHL-1, and FHR-1 and fH from other primates, 10 8 N. gonorrhoeae, were suspended in HBSS 2ϩ and incubated for 30 min at 37°C with 10% (v/v) heat-inactivated NHS or heat-inactivated serum from chimpanzee, baboon, and rhesus in a final reaction volume of 100 l. Bacteria were washed three times in HBSS 2ϩ , followed by digestion of bacterial pellets with 4ϫ lithium dodecyl sulfate sample buffer (NuPAGE LDS sample buffer; Invitrogen Life Technologies).…”

Section: Western Blottingmentioning

confidence: 99%

“…Certain Por1B gonococci can also bind chimpanzee C4BP. These strains also resist killing by normal chimpanzee serum (NChS) (39) and can be used successfully to infect chimpanzees experimentally.…”

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confidence: 99%

“…Attempts to infect or naturally colonize the genital tracts of several other animal species including baboons, pig-tailed macaques, monkeys (rhesus, squirrel, owl, and capuchin), marmosets, rabbits, and guinea pigs with N. gonorrhoeae have been unsuccessful (38). One mechanism that N. gonorrhoeae use to naturally infect humans is to bind human C4BP (a soluble-phase inhibitor of the classical pathway) rendering them selectively resistant to complement-mediated killing by NHS (39). Certain Por1B gonococci can also bind chimpanzee C4BP.…”

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confidence: 99%

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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

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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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“…The antigenic variability is also the major reason why there is still no vaccine against N. gonorrhoeae available. Furthermore, these bacteria also manage to inactivate or delude the complement system of human serum by recruiting the inhibitory complement component C4b-binding protein or by sialylation of their outer membrane lipooligosaccharide with host-derived cytidine 5 0 -monophosphate-N-acetylneuraminic acid (Mandrell and Apicella, 1993;Ngampasutadol et al, 2005;Putten, 1993).…”

Section: Ancestry and Evolution Of Ceacam3mentioning

confidence: 99%

CEACAM3: An innate immune receptor directed against human-restricted bacterial pathogens

Pils

Gerrard

Meyer

et al. 2008

International Journal of Medical Microbiology

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Carcinoembryonic antigen-related cell adhesion molecule 3 (CEACAM3) is an immunoglobulin-related glycoprotein exclusively expressed on granulocytes. In contrast to other members of the CEACAM family, CEACAM3 does not support cell-cell adhesion, but rather mediates the opsonin-independent recognition and elimination of a restricted set of human-specific Gram-negative bacterial pathogens including Neisseria gonorrhoeae, Haemophilus influenzae, and Moraxella catarrhalis. Within the last 4 years, molecular determinants of CEACAM3 function and CEACAM3-initiated signaling pathways have been elucidated. Sequence comparison between CEACAM3 and other CEACAM family members points to a chimeric origin of this receptor with the bacteriabinding extracellular domain and the function-promoting intracellular domain derived from different genes. This review summarizes the current knowledge about the structure-function relationship of CEACAM3 and tries to combine these molecular aspects with a plausible scenario concerning the evolutionary origin of this phagocyte receptor in the light of host-pathogen adaptation.

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Human C4b-binding protein selectively interacts withNeisseria gonorrhoeaeand results in species-specific infection

Cited by 84 publications

References 51 publications

Phenotypic characterization of OmpX, an Ail homologue of Yersinia pestis KIM

Phenotypic characterization of OmpX, an Ail homologue of Yersinia pestis KIM

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

CEACAM3: An innate immune receptor directed against human-restricted bacterial pathogens

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