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USE OF PATHOGENIC NON-HUMAN AND HUMAN STRAINS TO INVESTIGATE THE POTENTIAL SURVIVAL OF INFECTIVE HELICOBACTER BACTERIA
Impact/Purpose:
Develop animal based studies to better characterize infectivity in virulent strains of Helicobacter pylori. Determine if short-based studies such as repeated intraperitoneal exposures or multiple gavage exposures can be used to determine the capacity of strains to colonize tissues. Evaluate animal strains of Helicobacteras substitutes for H. pylori virulence capability in infectivity experiments.
Description:
Humans are the primary known reservoir for strains of Helicobacter pylori. Many factors concerning the infectivity of this microorganism among humans remain unknown. Significant associations have been reported between the presence of Helicobacter pylori in drinking water and human clinical infections. Comparative studies of the colonization efficiencies of different Helicobacter strains will provide further evidence concerning the virulence capabilities of these microorganisms. Current research suggests that there is heterogeneity among Helicobacter pylori in their ability to successfully colonize and infect human hosts. Viable forms of Helicobacter pylori are released in fecal material but the exact transmission between human hosts remains to be fully elucidated. The transmission of Helicobacter pylori by treated distribution water systems also remains in question. H. pylori is reported to exist in one of two general forms; a spiral-shaped vegetative form and a coccoid-shaped resistant form. Both types exhibit viable characteristics, but only the spiral shaped forms are culturable in the lab. Previous research methods used to detect the presence of this microorganism could not differentiate completely between viable and nonviable cells. Efforts to resuscitate or transform coccoid cells into spiral forms have been largely unsuccessful. Environmental chamber studies indicate that even
spiral forms become non-culturable when incubated in environmental waters. It is unclear whether either spiral or coccoid forms retain their infectivity after exposure to environmental waters. The inability of molecular-based assays to accurately monitor "coccoid forms" of Helicobacter will require other methodologies for determining infectivity capability. Nonculturable forms of microorganisms can often be revived by passage in host animals. We propose using a model involving immunocompromised mice to possibly resuscitate non-culturable forms of H. pylori to better determine their transmission in the environment. Animal studies are still the best method for validating virulence activities in bacteria. Recent mouse models of Helicobacter pylori-induced disease have been useful in elucidating virulence factors. Strains of Helicobacter used in mouse models include Helicobacter felis (a close relative of H. pylori) as well as a strain of H. pylori that will colonize mice (strain Sydney strain 1, SS1). An immunocompromised animal model will identify activities crucial in the process of H. pylori infections in humans. This type of mouse model study will also be useful in characterizing the strain-specific differences in virulence within Helicobacter pylori. This study will characterize host responses to different Helicobacter pylori strains. These types of animal studies are the most promising for detecting and monitoring the coccoid forms of Helibacter pylori currently unassayable by current molecular methodologies.