Dr. June R. Scott

The research interests of our lab focus on understanding how bacteria cause disease in humans. We have chosen the Gram positive organism ( Streptococcus pyogenes, the group A streptococcus or GAS) to study.

Regulation of virulence factors in the group A streptococcus
(Streptococcus pyogenes)

The GAS is an exclusively human pathogen that causes a broad range of diseases from the usually self-limiting "strep throat" to severe invasive infections ("the flesh eating bacterium") including the streptococcal toxic shock syndrome. Currently, all GAS strains are sensitive to penicillin, although the frequency of penicillin treatment failure appears to be increasing. Since some GAS strains can cause many different diseases, we believe that an understanding of the regulation of expression of the GAS virulence factors is critical to devising ways of combating this pathogen. We are currently focusing on the 2-component signal transduction system CovR/CovS which regulates expression of about 15% of the GAS genome either directly or indirectly. We are investigating how CovR binds to DNA (in collaboration with Gordon Churchward, Assoc. Prof., Microbiology Dept, Emory), how CovR regulates transcription, what regulates expression of covR and how this system responds to changes in the environment.

The role of mRNA decay in gene regulation in GAS

We recently identified a class of genes in GAS whose transcripts are more abundant in stationary than in exponential phase of growth. This is largely a result of the unprecedented stability of their transcripts at this growth stage. We also discovered that, unlike normal transcripts, decay of these transcripts in exponential phase depends on the 3'-5' exonuclease polynucleotide phosphorylase. We are currently investigating the structural features that make these transcripts unique and the enzymes in Gram-positive bacteria required for messenger RNA decay. This work should lead to a greater understanding of the pathobiology of the GAS, which is needed as the basis for development of more effective anti-infective therapy.

Surface Proteins in Gram⁺ bacteria and Pilus Assembly

The general mechanism for anchoring proteins to the cell wall of Gram-positive bacteria requires the transpeptidase sortase, which recognizes and cleaves a short amino acid motif preceding a C-terminal hydrophobic region and charged tail. We identified two sortases in the Group A streptococcus that anchor distinct subsets of proteins that have the same motif. One of these sets of proteins has been found to form a hair-like structure (pilus) on the bacterial surface that is responsible for attachment of the bacterium to its host. We are investigating the mechanism by which the sortase-like enzyme (pilin polymerase) covalently links the pilin proteins to each other and to the cell wall. We are also investigating the function of other proteins required for this process. Greater understanding of the mechanism of assembly of these adherence structures should provide new targets for antibacterial therapy and allow the design of new vaccine vectors.