“I decided to attend Wake Forest for graduate studies since the program is one of the best in the country for teaching me to become an independent scientist. The professors within the department are all very enthusiastic and approachable and there is great opportunity for collaboration among the different branches within the program.  The graduate students within the program all seem well satisfied.  I really like the closeness of the environment and feel like it will be a great research and learning experience.”

Srv regulation of SpeB and Group A Streptococcus biofilm formation

Group A Streptococcus (GAS) is a Gram-positive pathogen that is one of the most common causes of bacterial upper respiratory tract infections in all age groups.  Prompt diagnosis and treatment of GAS infection is necessary to avoid the potential development of acute rheumatic fever (ARF) and subsequent rheumatic heart disease (RHD); autoimmune inflammatory diseases brought on by cross-reactivity between streptococcal and human tissue antigens.  The only known reservoir of GAS is humans, and the organism is generally disseminated by individuals with symptomatic infection, although asymptomatic carriers also transmit the pathogen.  Recent evidence suggests that GAS may form biofilms, a community of microorganisms characterized by an adhesive and perhaps protective matrix.  Furthermore, we have discovered that inactivation of the streptococcal regulator of virulence (srv) significantly reduces the ability of GAS to form biofilms in vitro.  Initial evidence suggests that this biofilm deficient phenotype may be due to increased production of a potent streptococcal cysteine proteinase (SpeB) in the srv mutant strain.  Thus, our primary hypothesis is that the reduction of GAS biofilm formation observed following inactivation of srv is due to SpeB mediated cleavage of proteins required for biofilm attachment and aggregation.  Two Aims will address this hypothesis: (1) to determine at what level (transcription, translation, or secretion/maturation) Srv is regulating the production of mature SpeB and (2) to determine the role that Srv and SpeB play in GAS biofilm formation in vivo.  Upon completion of this project, we will have gained new insights into GAS pathogenesis and the role of GAS biofilms in disease.