Phase variation of lipopolysaccharide directs interconversion of invasive and immuno-resistant phenotypes of Neisseria gonorrhoeae.

Abstract

Phase variation of Neisseria gonorrhoeae lipopolysaccharide (LPS) controls both bacterial entry into human mucosal cells, and bacterial susceptibility to killing by antibodies and complement. The basis for this function is a differential sialylation of the variable oligosaccharide moiety of the LPS. LPS variants that incorporate low amounts of sialic acid enter human mucosal epithelial cells very efficiently, but are susceptible to complement‐mediated killing. Phase transition to a highly sialylated LPS phenotype results in equally adhesive but entry deficient bacteria which, however, resist killing by antibodies and complement because of dysfunctional complement activation. Phase variation of N. gonorrhoeae LPS thus functions as an adaptive mechanism enabling bacterial translocation across the mucosal barrier, and, at a later stage of infection, escape from the host immune defence.

Differential Salmonella survival against communities of intestinal amoebae

“…These outermost cellular structures are the most accessible to antibodies or white blood cells, so it is not surprising that they are quite variable among bacteria that interact with eukaryotes in this way. The need for systemic pathogens to escape immune recognition continually selects for new, rare antigenic types; here, FDS favours the newly different cells by allowing for prolonged infections or the reinfection of non-naïve hosts (Hosking et al, 1999;Jennings et al, 1995;Reeves, 1995;van Putten, 1993). Yet many non-pathogens are also antigenically diverse, and many pathogens -like Salmonella enterica -have antigenic diversity that is inconsistent with FDS (Wildschutte et al, 2004).…”

Analysis of the role of HP0208, a phase-variable open reading frame, and its homologues HP1416 and HP0159 in the biosynthesis of Helicobacter pylori lipopolysaccharide

“…Based upon cumulative information derived from phasevariable LPS genes in organisms such as Haemophilus influenzae (Weiser & Pan, 1998) and Neisseria gonorrhoeae (van Putten, 1993) it is reasonable to assume that phase variation of HP0208 contributes to the niche adaptation of H. pylori. Its precise role, however, awaits determination.…”

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

“…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).…”