Mechanisms of Mycoplasmal Disease Pathogenesis

University Of Alabama At Birmingham, Birmingham AL

Investigators

Linked publications & trials

Abstract

DESCRIPTION (provided by applicant): Mycoplasmas are widely distributed in nature and commonly produce diseases of considerable economic impact, yet little information is available concerning mechanisms of pathogenesis and effective methods of control are unavailable. Mycoplasmal species have the smallest known bacterial genomes, and the availability of the genome sequence of at least 7 different species is being used as a measure for determining the minimal gene set for cellular life. But the mycoplasmas are dependent on the animal host to obtain many vital nutrients. The mycoplasmas not only have the tools to be self-replicating organisms, they also are fully equipped for survival in the animal and often cause chronic disease of the respiratory and genital tracts and joints. We propose to exploit mycoplasmas as minimalist systems for studying how pathogens acquire nutrients from their host and combat host defenses for long-term survival. We choose to use Mycoplasma pulmonis as a model organism because it is a natural pathogen of mice, causing murine respiratory mycoplasmosis. Thus, host-pathogen interactions can be explored using a minimalist pathogen and the power of mouse genetics. The expectation is that such studies will have broad impact for understanding host-dependent bacterial pathogens. For Specific Aim 1, we propose to study carbohydrate transport and metabolism. Little is known about mycoplasmal metabolism and its regulation. We believe that the ability to acquire carbohydrates from the animal host is of central importance for in vivo survival of the mycoplasma. During the funding period of the current award, a transposon library of M. pulmonis has been characterized to reveal mutants in nearly 300 genes. For Specific Aim 2, we propose to identify transposon mutants that fail to survive in the mouse lung. Mutants that do not survive will be characterized further to determine whether their defect is a failure to grow in vivo, to adhere to the epithelium, or to resist host defenses.