Research in my laboratory is aimed at understanding how bacterial communities use extracellular cell-cell signaling molecules to coordinate biological processes as a group. This process, referred to as quorum sensing, is used by many bacteria to regulate a variety of biomedically-relevant processes including the production of virulence factors, the secretion of degradative enzymes, horizontal gene transfer, antibiotic production, cell motility, sporulation, genetic competence, and biofilm formation. Studying the regulation of the quorum response and dissecting the regulatory pathways controlled by cell-cell signaling in B. subtilis should aid in our general understanding of how pathogenic and non-pathogenic bacteria coordinate group behavior.
B. subtilis and its closest relatives have multiple rap-phr quorum sensing gene pairs that coordinate a variety of physiological processes with population density. Additional rap-phr gene pairs are present on mobile genetic elements including plasmids, conjugative elements, and bacteriophage; however, relatively little is known about their function. We recently discovered novel functions for plasmid-encoded Rap60-Phr60 in regulating sporulation, genetic competence, and biofilm formation. Moreover, two noncanonical roles were identified for Rap60 in regulating the activities of the response regulators Spo0A and ComA. Specifically, Rap60 regulates Spo0A, in part, by inhibiting the autophosphorylation of KinA, a sporulation-specific kinase. In contrast, Rap60 regulates the activity of ComA by forming a ternary complex with ComA and DNA that inhibits transcription activation of ComA-dependent genes. Current research is aimed at understanding the molecular function of other rap-phr pairs using a variety of approaches including molecular biology, transcriptional profiling, genetics, and biochemistry.
A second focus of my research is aimed at understanding how populations of B. subtilis sense and respond to extracellular cell-cell signaling molecules and metabolites produced from other soil microbes. We recently identified a novel iron chelating activity present in cultures of B. subtilis. Interestingly, several other bacteria including E. coli, P. aeruginosa, and B. anthracis produce a similar iron chelating activity that can be internalized by B. subtilis through a common uptake system. These findings are of significant biomedical importance because iron is an essential co-factor for many biological processes. Moreover, iron plays an important role in regulating the production of virulence factors and facilitating host colonization in many pathogenic bacteria.
Learn more at www.micro.umass.edu/faculty-and-research/kevin-griffith
- PhD University of Maryland Baltimore County, 2002
- Postdoctoral Training: Massachusetts Institute of Technology, 2008