Neisseria gonorrhoeae mutants altered in toxicity to human fallopian tubesand molecular characterization of the genetic locus involved

In an effort to identify potential cytotoxins expressed by Neisseria gonorr hoeae, we have identified a locus that, when mutated in the gonococcus, res ults in a significant increase in toxicity of the strain to human fallopian tube organ cultures (HFTOC). This locus, gly1, contains two open reading f rames (ORFs) which are likely cotranscribed. ORF1 encodes a polypeptide of 17.8 kDa with a signal sequence that is recognized and processed in Escheri chia coli and N. gonorrhoeae. The 15.6-kDa processed polypeptide has been o bserved in membrane fractions and filtered spent media from cultures of E. call expressing gly1 and in outer membrane preparations of wild-type N. gon orrhoeae. The gly1 locus is not essential for bacterial survival, and it do es not play a detectable role in epithelial cell adhesion, invasion, or int racellular survival. However, a gly1 null mutant causes much more damage to fallopian tube tissues than its isogenic wild-type parent. A strain comple mented in trans for the gly1 mutation showed a level of toxicity to HFTOC s imilar to the level elicited by the wild-type parent. Taken together, these results indicate an involvement of the gly1 locus in the toxicity of N. go norrhoeae to human fallopian tubes.