Systematic screens such as that mentioned above (Cronin et al., 2009) can also be used to identify host factors co-opted by a pathogen that, when mutated, render the host resistant to the pathogen. An example using a traditional genetic approach is the case of Vibrio cholerae, in which investigators showed that feeding V. cholerae bacteria to flies caused rapid death (i.e. in 2-3 days) that required the function of the primary virulence factor cholera toxin (CTX) (Blow et al., 2005) . CTX is an ADP ribosyl transferase that specifically ribosylates the Gs subunit of a host trimeric Gs protein, resulting in constitutive activation of adenylate cyclase (Middlebrook and Dorland, 1984) . The dependence on CTX was Host-pathogen interactions in Drosophila PERSPECTIVE unexpected because flies lack the enzymes required to synthesize the GM1 ganglioside that serves as the CTX receptor and that is present in most vertebrates and a few invertebrates. Accordingly, feeding flies purified CTX holotoxin had no effect (Blow et al., 2005) . Paradoxically, however, full virulence of ctx-mutant bacteria could be restored by feeding infected flies purified CTX, suggesting that, in the presence of the bacteria, a novel alternative route of CTX delivery to host cells in the gut might be employed. Further analysis showed that several host target factors known from mammalian studies were required by V. cholera to infect flies, such as proteins mediating the dehydrating effects of CTXdependent cAMP production -including a Gs subunit, adenylate cyclase and an SK-type potassium ion channel (Blow et al., 2005) . Having established flies as a model for V. cholerae infection, the authors then screened a large collection of stocks with mapped transposon insertions into the fly genome and identified mutations that either enhanced or reduced severity of infection. This strategy identified several host genes important for the response to V. cholerae infection, including those conferring resistance when mutated and that presumably are exploited by bacteria (e.g. components of the TNF and IMD pathways) as well as those used in host defense (e.g. the apoptotic pathway) (Berkey et al., 2009 ).