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Heparin protects Opa+ Neisseria gonorrhoeae from the bactericidal action of normal human serum
1Laboratory of Microbial Structure and Function, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, Hamilton, Montana 59840, USA.
Abstract:
The pathobiological significance of lipooligosaccharide (LOS) and outer membrane opacity protein (Opa) changes in gonorrheal disease are poorly understood. We assessed variants of strain MS11mk with different LOS and Opa phenotypes for their liability to killing by normal human sera. LOS differences correlated with strikingly disparate susceptibilities to serum killing; LOSa variants were serum resistant, LOSb variants were serum sensitive, and sialylation of LOSb variants enhanced their survival (as reported previously). Opa phenotype had little influence on the killing of serum-sensitive LOSb cells that were incubated directly in normal human sera, but preincubation of Opa+ LOSb variants in heparin increased their serum resistance whereas Opa- LOSb variants showed no change. Some Opa proteins conferred slightly higher resistance than others, but heparin preincubation increased serum resistance for variants expressing each of seven Opa proteins. These in vitro phenomena may relate to conditions within the male urethra where sulfate-containing proteoglycans are abundant and where antibody and complement may transude from blood plasma. The results suggest that the selective advantage for Opa+ Neisseria gonorrhoeae bacteria observed in vivo may reflect their ability to utilize host cell components to resist killing by host defenses.
Insights
Neisseria gonorrhoeae lipooligosaccharide (LOS) type significantly impacts serum resistance. Outer membrane opacity protein (Opa) enhances survival in the presence of heparin, potentially aiding bacterial defense in the male urethra.
Area of Science:
- Microbiology
- Immunology
- Pathogenesis
Background:
- The role of lipooligosaccharide (LOS) and outer membrane opacity protein (Opa) in gonorrheal disease pathogenesis is not fully understood.
- Understanding bacterial evasion mechanisms is crucial for combating Neisseria gonorrhoeae infections.
Purpose of the Study:
- To investigate the impact of different LOS and Opa phenotypes on the susceptibility of Neisseria gonorrhoeae to normal human serum killing.
- To explore potential mechanisms of serum resistance related to host-derived molecules.
Main Methods:
- Assessing serum resistance of Neisseria gonorrhoeae strain MS11mk variants with distinct LOS and Opa phenotypes.
- Evaluating the effect of heparin preincubation on the serum resistance of Opa-positive and Opa-negative variants.
Main Results:
- LOS variants exhibited differential susceptibility to serum killing, with LOSa variants being resistant and LOSb variants being sensitive.
- Sialylation of LOSb variants enhanced their survival.
- Opa phenotype had minimal impact on serum killing of LOSb variants directly in serum, but heparin preincubation significantly increased serum resistance in Opa+ variants.
Conclusions:
- Lipooligosaccharide type is a major determinant of Neisseria gonorrhoeae serum resistance.
- Outer membrane Opa proteins, particularly when exposed to heparin, can confer resistance to host immune defenses.
- These findings suggest that Neisseria gonorrhoeae may utilize host components like proteoglycans to evade immune clearance in vivo, contributing to its selective advantage.