Date of Award

Spring 2002

Document Type

Thesis

Department

Life & Environmental Sciences

First Advisor

Gerald Shields

Second Advisor

Sam Alvey

Third Advisor

Sean Reid

Abstract

Five genes that encode novel extracellular proteins were previously identified through the genomic analysis of four Group A Streptococcus strains (serotypes Ml, M3, M5, and M18) (Reid et al., 2001). Four of the five proteins have an LPXTG amino acid motif at the carboxyterminus, a motif that covalently links extracellular proteins to the cell surface in many gram-positive pathogens. All of the genes encode proteins with a secretion signal sequence at the aminoterminus. In vivo expression was demonstrated with Western blots using sera obtained from 80 patients with invasive infections, non-invasive skin infections, pharyngitis, and acute rheumatic fever. Real-time reverse transcriptase-PCR analysis of gene transcription showed that the amount and time of maximal gene transcript varies for the five genes among the Ml, M3, and M18 serotypes. With the use of flow cytometry, surface expression was confirmed for proteins for which antibodies were available. These results indicate that further exploration of these genes as potential vaccine candidates is warranted.

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