Defining the molecular basis of arthropod transmission of Bartonella species: identifying essential bacterial genes using a neo-natural experimental system and signature tagged mutagenesis. . (360G-Wellcome-079318_Z_06_Z)

Bartonella species are arthropod-transmitted haemoparasites of medical importance that exploit mammals (including humans) as reservoir hosts. Although early experimental studies concluded that the infectiousness of bartonellae towards their reservoirs was augmented by arthropod transmission, contemporary investigations of the molecular mechanisms underlying bartonella persistence in their vectors, particularly those underlying this apparent preparedness for infection, are lacking. To begin to ad dress this shortfall, we will develop a near-natural experimental transmission system in which Bartonella birtlesii infections will be established and monitored in captive Apodemus sylvaticus (the wood mouse, a natural reservoir host) and will be transmitted by fleas that comprise the natural wood mouse fauna (fleas are primary vectors for B. birtlesii). We will identify B. birtlesii genes that are required for bacterial persistence during inter-host transmission by determining the performance o f members of a library of signature tagged transposon mutants of B. birtlesii using the near-natural system. Mutants in which transmission-essential genes are disrupted will be identified by their absence in newly infected animals, then characterised.