Experimental human gonococcal urethritis: 250 Neisseria gonorrhoeae MS11mkC are infective
H Schneider1, A S Cross, R A Kuschner
1Department of Bacterial Diseases, Walter Reed Army Institute of Research, Washington, DC 20307-5100, USA.
Abstract:
Neisseria gonorrhoeae MS11mkA (mkA) expresses one 3.6-kDa lipooligosaccharide (LOS). Variant MS11mkC (mkC), expressing four larger LOSs, occurs in vitro among mkA at a frequency of 10(-3). Infectivity of these variants was compared in 2 groups of volunteers inoculated with approximately 40,000 piliated, Opa- gonococci of either strain. The mkC variant infected 5 of 5 while mkA infected only 2 (40%) of 5. Gonococci recovered from the mkA infections showed a transition toward the mkC LOS phenotype. The mkA inoculum contained approximately 40 mkC gonococci. These data confirmed earlier studies and suggested that small numbers of mkC gonococci would be infective. This hypothesis was tested in three more experiments. In two, volunteers were inoculated with 250 or 1250 mkC, infecting 3 of 7 in each group, and in the third, 1600 mkC infected 2 of 6, resulting in a total of 8 of 20 infected by < or = 1600 mkC. Gonococci shed by infected volunteers maintained the mkC LOS phenotype but shifted from Opa- to Opa+. Thus, LOS and opacity protein, as well as pilus, are gonococcal virulence factors.
Insights
The Neisseria gonorrhoeae variant MS11mkC, expressing larger lipooligosaccharides (LOS), is more infectious than MS11mkA. Even small numbers of mkC gonococci can cause infection, highlighting LOS and opacity proteins as key virulence factors.
Area of Science:
- Microbiology
- Infectious Diseases
- Bacteriology
Background:
- Neisseria gonorrhoeae exhibits phenotypic variation, including differences in lipooligosaccharide (LOS) expression.
- The MS11mkA strain expresses a single LOS, while the MS11mkC variant expresses multiple larger LOS molecules.
- In vitro studies suggested that the MS11mkC variant might possess increased infectivity compared to MS11mkA.
Purpose of the Study:
- To compare the infectivity of Neisseria gonorrhoeae MS11mkA and MS11mkC variants in a human volunteer model.
- To investigate the role of LOS phenotype and opacity (Opa) protein expression in gonococcal virulence.
- To determine the minimum infectious dose of the MS11mkC variant.
Main Methods:
- Human volunteers were inoculated with known quantities of piliated, Opa- Neisseria gonorrhoeae MS11mkA or MS11mkC strains.
- Infectivity was assessed by the development of clinical gonorrhea.
- Gonococci recovered from infected volunteers were characterized for LOS phenotype and Opa protein expression.
Main Results:
- The MS11mkC variant demonstrated higher infectivity than the MS11mkA strain (5/5 vs. 2/5 volunteers infected).
- Gonococci recovered from MS11mkA infections showed a phenotypic shift towards the MS11mkC LOS profile.
- Sub-infectious doses of MS11mkC (≤1600 organisms) were capable of causing infection (8/20 volunteers infected).
- Shed gonococci maintained the MS11mkC LOS phenotype but transitioned from Opa- to Opa+.
Conclusions:
- Lipooligosaccharide (LOS) structure is a critical determinant of Neisseria gonorrhoeae virulence.
- Opacity (Opa) proteins also contribute to gonococcal pathogenesis.
- Even small inocula of virulent variants can establish infection, underscoring their clinical relevance.
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