Newton Hillard, PhD Eastern Mexico Mexico newton.hilliard@enmu.edu Phone:(505) 562-2463 Personal Website

Title: Protein Structure-Function of Chromosomes in Gastric Microbial Pathogenisis

Project Description:

A number of pathogens such as H. pylori, Campylobacter sp. and Bacillus anthracis can cause serious and even lethal disease states in humans and other mammals by invading the host through the highly acidic environment of the stomach. While the post-colonization defense mechanism used by the individual organisms to survive this hostile environment may be known and relatively well characterized (e.g. on, acid neutralization, and/or motility through the mucosal pH gradient), it is not as clear how the organisms survive the 'transit time' necessary to invade gastric/intestinal tissues and establish those conditions favorable to pathogenesis. Indeed, it is well known that both Campylobacter jejuni and Helicobacter pylori can both be killed by brief exposure to HCl at pH < 4.0. During the transit time, periplasmic, plasma membrane peripheral and/or outer membrane proteins could be exposed to an HCl rich environment with a pH of 2.0 or below for significant periods of time (i.e. minutes to hours). This raises the question as to how these organisms survive the transit time.

Long-term goals of the research are to elucidate the mechanism of electron transfer and subsequent microbial energy conservation in highly acidic environments.

Specific Aims:
AIM 1: Elucidation of protein structural elements which afford biological structural integrity at low pH.
AIM 2: Elucidation of the mechanism which allows electrostatic docking of cytochromes, and subsequent electron transfer, at pH extremes.