Of the15 species of Neisseria that inhabit human mucosal surfaces, only are pathogens; the others are commensals that form part of our normal flora. In light of recent reports that commensal bacteria can inhibit pathogen colonization, we determined whether commensal Neisseria elongate has the ability to antagonize pathogen Neisseria gonorrhoeae in vitro and in vivo. To summarize our findings, Neisseria elongate dramatically lowers the viability of N. gonorrhoeae during co--?culture in vitro. The lethal agen, which is in the medium, is Neisseria elongate chromosomal DNA, and killing of N. gonorrhoeae requires its uptake by the pathogen in a Type IV pilus/DUS dependent manner. Moreover, N. elongate accelerates the clearance of N. gonorrhoeae from mice. We hypothesize that the N. elongate genome harbors a locus/loci which, when taken up by N. gonorrhoeae, is lethal to the pathogen. We further hypothesize that uptake of N. elongate DNA by N. gonorrhoeae is the mechanism by which the pathogen is rapidly cleared from mice. We propose two Specific Aims to test these hypotheses in vitro and in vivo..
We discovered that Neisseria elongata, a commensal, dramatically reduces the viability of pathogen Neisseria gonorrhoeae during co?culture in vitro. The lethal agent is N. elongate chromosomal DNA, which actively growing Neisseria elongate cultures apparently release/secrete into the medium. N. elongate DNA kills N. gonorrhoeae when it is taken up by the pathogen in a Type IV pilus dependent manner. Consistent with this in vitro antagonistic behavior of N. elongata, our collaborator, Dr. Ann, Jerse (USUHS), discovered that N. elongate rapidly clears N. gonorrhoeae from co?infected mice. The aims of this R21 project are 1) to identify the locus/loci in the N. elongate genome that is lethal to N. gonorrhoeae, and 2) to determine whether a N. gonorrhoeae DNA uptake mutant is resistant to clearance from mice by N. elongata.
