Molecular basis for serum resistance in Neisseria gonorrhoeae

Rice, Peter A.

doi:10.1128/cmr.2.suppl.s112

Cited by 67 publications

(30 citation statements)

References 61 publications

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“…A large proportion of human bactericidal antibodies are to LOS epitopes, and its structure influences the bacter~olytic effects of human serum on GC. Some GC strains when grown in vitro are not killed by human serum (Ser R) and are common among isolates from patients with disseminated GC infection (17). However, most GC strains are sensitive (SerS).…”

Section: Discussionmentioning

confidence: 99%

Variation of gonococcal lipooligosaccharide structure is due to alterations in poly-G tracts in lgt genes encoding glycosyl transferases.

Yang

Gotschlich

1996

The Journal of Experimental Medicine

117

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SUlTlnlaryThe lipooligosaccharide (LOS) expressed by gonococci spontaneously varies its structure at high frequency, but the underlying genetic mechanism has not been described. We have previously reported that the genes encoding the glycosyl transferases responsible for the biosynthesis of the variable o~ chain of the LOS of Neisseria gonorrhoeae are located in a locus containing five genes, lgtA, lgtB, IgtC, IgtD, and lgtE. Sequence analysis showed that tgtA, lgtC, and IgtD contained poly-G tracts within the coding frames, leading to the hypothesis that shiftsin the number of guanosine residues in the poly-G tracts might be responsible for the.high frequency variation in structure of gonococcal LOS. We now provide experimental evidence confirming this hypothesis.

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Section: Discussionmentioning

confidence: 99%

Variation of gonococcal lipooligosaccharide structure is due to alterations in poly-G tracts in lgt genes encoding glycosyl transferases.

Yang

Gotschlich

1996

The Journal of Experimental Medicine

117

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“…Neisseria gonorrhoeae, an important cause of sexually transmitted disease, also recruits fH to its cell surface. Isolates of N. gonorrhoeae can be classified as serum sensitive or serum resistant (SR) on the basis of their resistance against complementmediated killing (13). fH appears to bind to two distinct targets on N. gonorrhoeae (14).…”

mentioning

confidence: 99%

Functional Significance of Factor H Binding toNeisseria meningitidis

Schneider

Exley

Chan

et al. 2006

The Journal of Immunology

220

197

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Neisseria meningitidis is an important cause of septicemia and meningitis. To cause disease, the bacterium must successfully survive in the bloodstream where it has to avoid being killed by host innate immune mechanisms, particularly the complement system. A number of pathogenic microbes bind factor H (fH), the negative regulator of the alternative pathway of complement activation, to promote their survival in vivo. In this study, we show that N. meningitidis binds fH to its surface. Binding to serogroups A, B, and C N. meningitidis strains was detected by FACS and Far Western blot analysis, and occurred in the absence of other serum factors such as C3b. Unlike Neisseria gonorrhoeae, binding of fH to N. meningitidis was independent of sialic acid on the bacterium, either as a component of its LPS or its capsule. Characterization of the major fH binding partner demonstrated that it is a 33-kDa protein; examination of insertion mutants showed that porins A and B, outer membrane porins expressed by N. meningitidis, do not contribute significantly to fH binding. We examined the physiological consequences of fH bound to the bacterial surface. We found that fH retains its activity as a cofactor of factor I when bound to the bacterium and contributes to the ability of N. meningitidis to avoid complement-mediated killing in the presence of human serum. Therefore, the recruitment of fH provides another mechanism by which this important human pathogen evades host innate immunity.

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“…These bacterial components affect CЈ activity by a variety of ways, such as spatially hindering the binding of CЈ proteins (49) or antibodies (15) to the bacterial membrane, by binding "blocking" antibodies (58), by facilitating the inactivation of the CЈ cascade through the binding of negative regulators of CЈ (2,37,52,53,55,56), by preventing the productive insertion of the membrane attack complex into the outer membrane (OM) (24,30), or by interfering with opsonophagocytosis (71).…”

mentioning

confidence: 99%

A Novel Lectin, DltA, Is Required for Expression of a Full Serum Resistance Phenotype inHaemophilus ducreyi

Leduc¹,

Richards

Davis

et al. 2004

Infect Immun

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Haemophilus ducreyi, the causative agent of chancroid, is highly resistant to the complement-mediated bactericidal activity of normal human serum (NHS). Previously, we identified DsrA (for ducreyi serum resistance A), a major factor required for expression of the serum resistance phenotype in H. ducreyi. We describe here a second outer membrane protein, DltA (for ducreyi lectin A), which also contributes to serum resistance in H. ducreyi. Isogenic dltA mutants, constructed in 35000HP wild-type and FX517 dsrA backgrounds, were more susceptible to the bactericidal effects of NHS than each respective parent, demonstrating the additive effect of the mutations. Furthermore, expression of dltA in H. influenzae strain Rd rendered this highly susceptible strain partially resistant to 5% NHS compared to a vector-control strain. Although primary basic local alignment search tool analysis of the dltA open reading frame revealed no close bacterial homologue, similarity to the ␤-chain of the eukaryotic lectin ricin was noted. DltA shares highly conserved structural motifs with the ricin ␤ chain, such as cysteines and lectin-binding domains. To determine whether dltA was a lectin, ligand blots and affinity chromatography experiments were performed. DltA was affinity purified on immobilized lactose and N-acetylgalactosamine, and N-glycosylated but not glycosidase-treated model glycoproteins bound DltA. These data indicate that DltA is a lectin with specificity for lactose-related carbohydrates (CHO) and is important for H. ducreyi serum resistance.

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Molecular basis for serum resistance in Neisseria gonorrhoeae

Cited by 67 publications

References 61 publications

Variation of gonococcal lipooligosaccharide structure is due to alterations in poly-G tracts in lgt genes encoding glycosyl transferases.

Variation of gonococcal lipooligosaccharide structure is due to alterations in poly-G tracts in lgt genes encoding glycosyl transferases.

Functional Significance of Factor H Binding toNeisseria meningitidis

A Novel Lectin, DltA, Is Required for Expression of a Full Serum Resistance Phenotype inHaemophilus ducreyi

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