Figure 1. Inhibitors of hubs of human disease networks.

(a) Depiction of the concept where multiple pathogenic pathways overlap, and hub proteins (blue circles) mediate multiple disease pathways. This model proposes a drug screen design to look for compounds that simultaneously inhibit the function of the hub proteins and reduce cellular lethality caused by multiple pathogenic pathways. (b) A depiction of the design of the current study. The known host pathways and host proteins exploited by pathogens (HPEP) are considered. HapMap cell lines are used to study the association between cellular sensitivity to Pseudomonas aeruginosa exotoxin A (PE) and genetic mutations in genes coding for proteins exploited by PE. Mutations in host caspases are associated with altered sensitivity to PE, and these proteins are defined as disease network hubs, which will be used as targets for the following drug screens. This approach yields the broad-spectrum, host-oriented drug, Bithionol.