Tribal Warfare: Killing of pathogen N. gonorrhoeae by commensal N. elongata

 描述(申请人提供)：在生活在人类粘膜表面的15种奈瑟氏菌中，只有病原体；其他的是形成我们正常菌群一部分的共生体。鉴于最近有关共生细菌能抑制病原体定植的报道，我们在体外和体内确定了共生细长奈瑟菌是否具有拮抗病原体淋病奈瑟菌的能力。综上所述，在体外共培养过程中，细长奈瑟氏菌显著降低了淋球菌的生存能力。致死剂是细长奈瑟氏菌的染色体DNA，杀死淋球菌需要病原体以IV型菌毛/DUS依赖的方式摄取它。此外，细长奈瑟氏菌可加速淋病奈瑟菌从小鼠体内的清除。我们假设，细长淋球菌基因组含有一个或多个基因座，当淋球菌携带该基因座时，该基因座对病原体是致命的。我们进一步假设，淋病奈瑟菌对细长奈瑟氏菌DNA的摄取是病原体从小鼠体内迅速清除的机制。我们提出了两个特定的目标来在体外和体内验证这些假说。

 DESCRIPTION (provided by applicant): 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..