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Name:	Philip N. Rather
Position:	Associate Professor of Microbiology and Immunology Associate Professor of VA Medical Center
Degree:	Ph.D., Emory University, 1989
Programs:	MMG, Full Member
Phone:	404 728-5079
Address:	VA Medical Center, 1670 Clairmont Rd, 1940-001-1AD
Email:	prather@emory.edu
Research Descriptions:
Short:	Mechanisms of cell to cell signaling and quorum sensing in bacteria.
Long:	My research program focuses on the mechanisms of cell-to-cell communication in bacteria. In recent years, a large number of studies have revealed that the ability of bacteria to communicate with each other is far more widespread and complex than previously realized. This cell-to-cell communication or signaling is mediated by molecules termed autoinducers or pheromones and include: N-acyl homoserine lactones, small peptides, and furanones. Cell-to-cell signaling is a fundamental requirement for a number of bacterial processes. Of particular medical importance is the ability of cell-to-cell signaling to regulate virulence gene expression and biofilm formation in various pathogens. Biofilms are complex microbial communities that typically form on solid surfaces. Mature biofilms form a three-dimensional structure composed of cells surrounded by a polysaccharide matrix. Within the biofilm, aqueous channels are present that act to bring in nutrients and carry out waste products. In many ways, these remarkable bacterial structures resemble a simple tissue. Biofilms are of great medical importance. First, the formation of biofilms on indwelling devices such as catheters or artificial joints often contributes to the establishment of infections. Second, cells within a biofilm are highly resistant to antibiotics. This increased resistance is due, at least in part, to physiological differences in biofilm associated cells versus cells in a planktonic state. Biofilms are also present in tissues at the site of infections. In fact, the ability of antibiotics to effectively treat many chronic infections (lung infections in cystic fibrosis patients, sinusitis, prostatitis, middle ear infections) is severely compromised by biofilm formation in tissues. My lab is interested in the fundamental mechanisms of cell-to-cell signaling in Escherichia coli and Proteus mirabilis. A combination of genetic and biochemical approaches are used to answer the following questions: (i) what are the signals used for cell-to-cell communication, (ii) what genes are required for productions of, and response to these signals, and (iii) what role do cell-to-cell signaling pathways have in the physiology of each organism. Recently, we have identified a novel mechanism for cell-to-cell signaling that requires a new family of proteins, termed rhomboid, that are found in both prokaryotes and eukaryotes. The rhomboid proteins are novel intramembrane serine proteases that cleave a second protein to release a fragment that ultimately becomes a peptide-like signaling molecule. The E. coli rhomboid GlpG is being characterized in my lab. GlpG is required for the production of a peptide-like signaling molecule. Currently, we are characterizing the rhomboid-dependent signal from E. coli. A biologically similar, if not identical, signal is also produced by Proteus mirabilis.