Gonorrhea is the most frequently reported communicable disease in the United States, with an annual incidence of nearly one million cases. In a small but significant proportion of cases, one to two percent, the infection disseminates from the original site to produce bacteremia which is commonly followed by gonococcal arthritis (GCA). In fact, GCA is the most common cause of septic arthritis in young adults. Because patient compliance is poor and treatment failure may result in more serious sequelae, hospitilization is usually necessitated. Strains of Neisseria gonorrhoeae causing disseminated gonococcal infection (DGI) are highly resistant to the bactericidal activity of normal human serum (NHS), whereas non-disseminating strains are quite sensitive to NHS. Alteractions in both lipopolysaccharide and outer membrane proteins have been observed in DGI strains, but considerable debate exists as to the relative significance of each of these surface alterations in mediating resistance to NHS. It is easy to envision in vivo serum resistance in the gonococcus to be multifactoral, being the sum total of a series of phenotypic changes. For example, a difference in the composition of the LPS of the organism could create charge differences on the membrane surface that would alter the conformation of orientation of the surface proteins, creating or exposing new epitopes. Using chromosomal DNA from a DGI strain and an E. coli vector, we have prepared a recombinant plasmid, pWM3, which confers resistance to NHS upon a serum sensitive, non-DGI strain of N. gonorrhoeae (F62), but not upon E. coli. We will use these cloned genes to study one mechanism by which N. gonorrhoeae may resist the bactericidal affects of human serum. The experiments proposed for the first three years of this research, along with projects described for future years, are directed at answering several broad questions. 1. What are the cloned gene products and where are they located in N. gonorrhoeae? 2. How do the cloned gene products contribute to serum resistance? 3. Is this mechanism of serum resistance common among DGI isolates? 4. Is it possible and desirable to prepare DNA probes or vaccine antigens directed specifically aginst serum resistant gonococci?
| McShan, W M; Williams, R P; Hull, R A (1987) A recombinant molecule from a disseminating strain of Neisseria gonorrhoeae that confers serum bactericidal resistance. Infect Immun 55:3017-22 |
