Open Access Dissertation
Date of Award
Immunology and Microbiology
Melody N. Neely
CELL ENVELOPE MODIFICATIONS BY LCP FAMILY PROTEINS OF GROUP B STREPTOCOCCUS AND VIRULENCE SIGNALING BY PEPTIDES OF THE SALIVARICIN LOCUS OF STREPTOCOCCUS PYOGENES
HANNAH MORRISON ROWE
Advisor: Dr. Melody Neely
Major: Immunology and Microbiology
Degree: Doctor of Philosophy
Streptococci are important human and animal pathogens. Group B Streptococcus (GBS) is a zoonotic pathogen that is the leading cause of human neonatal sepsis and meningitis. In order to cause systemic disease GBS must produce a polysaccharide capsule. Capsule expression is controlled in part by the protein CpsA. We demonstrate that deletion of the cpsA gene, or expression of proteins with modifications to the extracellular or leucine zipper domains leads to reduced capsule expression and abnormalities in the bacterial cell wall and in cell division. Capsule and cell wall/cell division phenotypes are also seen when modified proteins are expressed in a wild type bacterial strain, indicating the modified protein exerts a dominant negative effect. Additionally, we demonstrate that the dominant negative effect can act through addition of purified modified CpsA protein or synthetic CpsA-derived peptide to wild type cultures. Further investigation of mutation of the lytR gene, which encodes for a protein related to CpsA, showed that LytR also has roles in bacterial capsule expression and cell wall/cell division phenotypes. Streptococcus pyogenes is a human pathogen that causes a range of diseases from superficial to life threatening. Peptide signaling serves important roles in many pathogenic bacterial species. We demonstrate that the peptides encoded in the salivaricin locus by S. pyogenes, SalA and SalZ, have key roles in controlling virulence of S. pyogenes. Data suggests that the SalA peptide acts synergistically with the two component signaling system also encoded in the sal locus, SalKR, in regulation of transcription and in survival in a model of septic infection. The SalZ peptide was also shown to have roles in transcription of the sal locus and virulence of S. pyogenes. Taken together, the work described here demonstrates key mechanisms for pathogenesis by Streptococci.
Rowe, Hannah Morrison, "Cell Envelope Modifications By Lcp Family Proteins Of Group B Streptococcus And Virulence Singaling By Peptides Of The Salivaricin Locus Of Streptococcus Pyogenes" (2014). Wayne State University Dissertations. 1099.