Exploring and exploiting the minor pilins of Type IV pili

Gram-negative bacteria are naturally resistant to large antibiotics in large part because of their impermeable outer membrane. Type IV pili (T4P) are surface-displayed filamentous polymers of major pilin proteins that have the ability to pull substrates through the outer membrane via retraction. T4P have one or several low-abundance minor pilins that localize to the tip of the pilus, mediating functions such as DNA binding and uptake. We hypothesize that minor pilins can be exploited as targets for drug delivery, facilitating the uptake of drugs across the bacterial outer membrane. Here I expressed and purified putative tip-associated minor pilins from important human pathogens and collected x-ray diffraction data on one of these, PilX from Neisseria gonorrhoeae. Additionally, we conclusively identify the Vibrio cholerae minor pilin, TcpB, at the tip of its pilus and use it to screen a phage display library in search of potential carrier molecules.