2017
DOI: 10.1093/femspd/ftx049
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Abstract: One sentence summary: Lipooligosaccharide sialic acid, a key virulence factor for gonococci, can be targeted by novel immunotherapeutics to overcome multidrug-resistant gonorrhea. Editor: Alison Criss ABSTRACTGonorrhea has become resistant to most conventional antimicrobials used in clinical practice. The global spread of multidrug-resistant isolates of Neisseria gonorrhoeae could lead to an era of untreatable gonorrhea. New therapeutic modalities with novel mechanisms of action that do not lend themselves to … Show more

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Cited by 23 publications
(25 citation statements)
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“…Generation of antibodies with bactericidal activity against unsialylated gonococci present during infection still has merit. LOS sialylation of gonococci in vivo probably covers excess sialylation, which may block invasion of gonococci into mucosal epithelial cells but protects the organism from natural host immunity, to loss of sialic acid modification, which conversely makes the gonococcus more invasive but more susceptible to eradication by host immune mechanisms ( 48 ). Furthermore, Schneider and colleagues ( 49 ) used a human male challenge model to demonstrate that gonococci with sialylated LOS were less infective than gonococci with nonsialylated LOS.…”
Section: Discussionmentioning
confidence: 99%
“…Generation of antibodies with bactericidal activity against unsialylated gonococci present during infection still has merit. LOS sialylation of gonococci in vivo probably covers excess sialylation, which may block invasion of gonococci into mucosal epithelial cells but protects the organism from natural host immunity, to loss of sialic acid modification, which conversely makes the gonococcus more invasive but more susceptible to eradication by host immune mechanisms ( 48 ). Furthermore, Schneider and colleagues ( 49 ) used a human male challenge model to demonstrate that gonococci with sialylated LOS were less infective than gonococci with nonsialylated LOS.…”
Section: Discussionmentioning
confidence: 99%
“…As this happens, each can become more sophisticated and the implications of any observations will be more effectively understood in the context of gonococcal infection and immunity. For example, ongoing efforts to “humanize” the mouse rely on cell line and primary cell-based efforts to understand gonococcal association with human cellular receptors (94), as well as blood-based studies to understand its ability to avoid serum bactericidal activity (208). Similarly, ongoing efforts to understand and then exploit gonococcal genetics have allowed in vitro microbiological approaches to reveal metabolic and drug resistance mechanisms that have led to studies in the established experimental human infection models (188, 209).…”
Section: Summary and Future Directionsmentioning
confidence: 99%
“…The resulting fusion protein acts by blocking binding of FH to the microbial surface, while the Fc domain activates complement, which in turn can result in the insertion of lytic membrane attack complexes to kill Gram-negative bacteria or engage Fc receptors and complement receptors for C3 fragments on phagocytes. We have demonstrated the efficacy of a chimeric protein where FH domains 18 through 20 are fused to Fc against N. gonorrhoeae (39,41,76). Based on the finding that N. gonorrhoeae also binds FH domains 6 and 7, we have fused these two domains with human IgG1 Fc to create FH SCR6-7/Fc.…”
Section: Discussionmentioning
confidence: 99%