Gonococcal lipooligosaccharide sialylation prevents complement-dependent killing by immune sera.

Area of Science:

• Microbiology
• Immunology
• Bacteriology

Background:

• Neisseria gonorrhoeae uses lipooligosaccharide (LOS) modification for immune evasion.
• Sialylation of LOS with 5'-CMP-N-acetylneuraminic acid confers resistance to normal human serum.
• This resistance is attributed to blocking bactericidal antibody binding to LOS.

Purpose of the Study:

• To investigate if sialylation of gonococci extends resistance beyond normal serum to immune sera.
• To determine if sialylation affects antibody binding to other outer membrane components.
• To assess the impact of sialylation on opsonophagocytosis and complement-mediated bacterial killing.

Main Methods:

• In vitro sialylation of Neisseria gonorrhoeae using 5'-CMP-N-acetylneuraminic acid.
• Assessing bacterial resistance to bactericidal activity of normal and immune human sera.
• Performing antibody absorption assays with sialylated and wild-type organisms against antibodies to Protein I.
• Evaluating opsonophagocytosis using antigonococcal antisera.

Main Results:

• Sialylated gonococci exhibited resistance to bactericidal effects of immune sera, not just normal serum.
• Sialylation did not prevent antibody binding to the major outer membrane protein (Protein I).
• Sialylated gonococci showed reduced opsonophagocytosis by antigonococcal antisera.
• The findings suggest sialic acid negatively impacts the complement pathway.

Conclusions:

• Gonococcal sialylation confers broad resistance to bactericidal antibodies and immune serum.
• Sialic acid on gonococci interferes with complement-mediated killing and opsonophagocytosis.
• This modification is a significant mechanism for Neisseria gonorrhoeae immune evasion.