Michael G. Caparon, Jr. Ph.D.

DEPARTMENT OF Molecular Microbiology
Keywords: bacteriology, gene expression, inflammation, microbial pathogenesis, toxin

Research in my laboratory is directed at understanding the interaction of pathogenic Gram-positive bacteria and their human hosts. Of particular interest is Streptococcus pyogenes, the causative agent of diseases including strep throat, scarlet fever and rheumatic fever.

Signaling interactions between the microbe and host cells are a focus, including how the host environment influences regulation of genes and how the streptococcus secretes proteins that influence the behavior of host cells. As a model of environmental regulation, state-of-the-art genetic and transcription profiling approaches in combination with animal models of infection, including a novel streptococcus-zebrafish model of host-pathogen interaction are used to examine how the streptococci respond to oxidative stress and the role this response contributes to the interaction with host cells in inflamed tissues.

Signaling interactions are influenced by the large number of protein toxins secreted by the streptococcus. However, mechanisms of protein secretion and folding are not well understood in Gram-positive bacteria. Through analysis of a secreted protease, we have discovered several components of a unique gene expression, secretion and processing pathway required for biogenesis of an active extracellular protease.

Finally, in analyzing how streptococci manipulate the signaling responses of host cells, we have identified cytolysin-mediated translocation, a novel pathway for the injection of streptococcal proteins directly into the cytosol of host cells. At least one of the translocated proteins has characteristics of a eukaryotic signal transduction factor. This pathway may be widespread among Gram-positive pathogens and be the functional equivalent of a type III secretion pathway.