All ETDs from UAB

Advisory Committee Chair

Kevin Dybvig

Advisory Committee Members

David E Briles

Daniel Bullard

John F Kearney

Warren L Simmons

Document Type

Dissertation

Date of Award

2012

Degree Name by School

Doctor of Philosophy (PhD) Heersink School of Medicine

Abstract

Mycoplasma pulmonis is a murine respiratory pathogen and is used as a model for studying chronic mycoplasmal respiratory disease. This organism has been used by many in vivo and in vitro studies to gain a better understanding of host-pathogen interactions in chronic respiratory infection. Studies have shown that alveolar macrophages play an important role in the removal of this pathogen from the host. Given that M. pulmonis is able to produce a chronic disease state, this organism should produce antiphagocytic factors that aid in avoidance of killing by alveolar macrophages. The Vsa proteins are involved in the avoidance of killing by complement and in modulating the ability of the mycoplasma to form a biofilm. These proteins contain an extensive tandem repeat region, a pattern seen in several other microbial proteins. The length of the tandem repeat unit varies from as few as 11 amino acids to as many as 19. The number of tandem repeats can be as high as 60 and varies at a high frequency due to slipped-strand mispairing events that occur during DNA replication. Capsular polysaccharides are involved in host immune avoidance in several other bacterial species. The EPS-I polysaccharide is produced on the surface of M. pulmonis and is made up of the monosaccharides glucose and galactose in a 1:1 ratio. Few mycoplasma polysaccharides have been described and little is known about their role in pathogenesis. We hypothesize that the Vsa proteins and the surface polysaccharide EPS-I would function as antiphagocytic factors. We show that cells producing a Vsa protein with many tandem repeats are relatively resistant to killing by alveolar macrophages. We also show that mutants lacking the EPS-I polysaccharide are more susceptible to binding and subsequent killing by macrophages. These results may be pertinent to understanding the function of proteins similar to Vsa in other microbes and suggest that polysaccharides produced by other species of mycoplasma are involved in immune avoidance. The results give further insight into how mycoplasmas are able to avoid the host immune system and sustain a chronic infection.

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