Cholera is characterized by severe diarrhea that can be fatal within hours at its worst. One of the most important steps in the infection process of V. cholerae is for the bacterium to colonize the human intestine by secreting a colonization factor called TcpF, though the exact mechanism behind this secretion remained elusive. Now, in a study that will be published soon in, researchers used X-ray crystallography, physicochemical analyses, and structural modeling to reveal exactly how V.
"It was known that the Toxin-coregulated pilus , a type 4 pilus system, played a crucial role in TcpF secretion, but the exact interaction between the two was unclear," says Hiroya Oki, lead author of the study. Pili are filament-like structures on the surface of bacterial cells that can have a multitude of functions. The V.
"We observed that TcpF trimerized into a flower-like unit to bind to the TcpB trimer at the end of the pilus," explains Shota Nakamura, senior author of the study."Importantly, we identified separate conserved domains that are vital for binding of TcpF to TcpB and TcpF trimerization, both of which are required for V. cholerae colonization.
Left: Model of the Type IV pilus system transporting the soluble colonization factor. Right: Crystal structure of TCP in complex with the colonization factor. Credit: 2022 Oki et al.,When considering their findings in context with other published works, the group hypothesized a model of secretion where TCP carries TcpB-bound TcpF out of the cell, after which TcpF dissociates from the pilus and moves freely in the human intestine, initiating the early stages of V.
The article,"Structural basis for the toxin-coregulated pilus-dependent secretion of Vibrio cholera colonization factor," will be published in