Peptidyl-prolyl cis-trans isomerases (PPIases) and virulence.
The ability of S. aureus to cause disease is largely due to an extensive repertoire of secreted and cell wall associated proteins, including adhesins, toxins, exoenzymes, and superantigens. These virulence factors, once produced, are typically transported across the cell membrane by the Sec secretion system in a denatured state. Once outside the cell, they must refold into their active form. This refolding step often requires the assistance of bacterial proteins, such as peptidly-prolyl cis-trans isomerases (PPIases). PPIases are enzymes that assist in the folding of proteins containing proline residues. One of the best-studied bacterial PPIases is the PrsA protein in Listeria monocytogenes. In L. monocytogenes PrsA contributes to pathogenesis by refolding secreted toxins and virulence factors. In the absence of PPIase activity proteins are misfolded or inactive. In the Carroll Lab we are interested in examining the role that PPIases play in protein secretion in S. aureus. We have identified two PPIases that contribute to virulence factor production, PrsA a cell-wall associated lipoprotein, and PpiB, a cytoplasmic PPIase. We are characterizing the role that each of these PPIases plays in S. aureus virulence factor secretion and pathogenesis.
S. aureus small RNAs (sRNAs)
Appropriate regulation of gene expression is critical to allow bacteria to cause disease within the host organism. A class of regulatory molecules (called small RNAs or sRNAs) has recently emerged as being important for virulence in S. aureus. The study of sRNAs in S. aureus is a relatively new and rapidly expanding field. Hundreds of sRNAs have been identified, however for most of them (including the well-studied regulator RNAIII), the locations of the sRNA genes are not included in S. aureus genome annotation files. One consequence of this oversight is that the existence of sRNAs is often overlooked. To address this situation and to facilitate improved detection and analysis of sRNAs in S. aureus we performed a comprehensive re-annotation of the S. aureus genome in which all previously identified sRNAs were mapped to their reported chromosomal locations. The re-annotated Genbank genome files created in this study contain annotations for 303 sRNA genes on the genome of the CA-MRSA strain USA300. The same strain contains only 135 transcription regulatory proteins. The revelation that sRNAs greatly outnumber regulatory proteins underlies the importance of this class of molecules to the bacterial cell. In the Carroll Lab we are interested in studying sRNAs to discover the roles they play in the bacterial cell.
Research in the Carroll Lab
Research in my laboratory is focused on exploring the mechanisms that allow Staphylococcus aureus to cause disease in humans. Infections caused by S. aureus, and in particular those caused by the highly drug resistant form, methicillin resistant S. aureus (MRSA), are a growing problem in the United States and very few antibiotics remain effective in treating diseases caused by this bacteria. Understanding the pathogenesis of S. aureus is critical to aid the development of effective vaccines and treatments.