Areas of Research
- Host:pathogen Interaction
The primary initiative of the human microbiome project is to increase our understanding of the structure and function of indigenous microbiota, and their effects on human health and predisposition to disease. One of the best-understood human-associated microbial communities is the oral microbiome. This biofilm (dental plaque) maintains its structure and function through a complex array of bacterial cell-cell and cell-host communication networks. Studies have shown that within the oral cavity there is a succession of select microbial interactions that directs the maturation of this extremely complex, yet defined community structure. Although the initiating factors that lead to development of periodontal diseases are not clearly defined, in many individuals there is a fundamental shift from a health-associated microbiome to one that is pathogenic in nature and a central player in this shift is the strict anaerobe Porphyromonas gingivalis. This bacterium is the primary model organism studied in the Davey lab.
A recent series of studies indicates that P. gingivalis can transform a benign microbial community to a pathogenic one leading to inflammatory periodontal bone loss, indicating that its pathogenic potential is dependent on both its physiological state and its intercellular interactions within the oral microbial community. Hence, P. gingivalisis best thought of as a pathobiont, i.e. an indigenous member of the human microbiota that under certain perturbations to the host and/or microbiome can cause pathology. As a pathobiont, its ability to colonize and express virulence determinants is central to its ability to trigger disease. Using a combination of molecular genetics, bacterial physiology, and biochemical techniques; the Davey lab is focused on determining the mechanisms that control the emergence of its pathogenic state. It is evident that changes in expression of surface structures (e.g. capsule, LPS, and fimbriae) play an important role in this switch. The Davey lab has discovered that a histone-like DNA-binding HU protein plays a key role in coordinating the expression of surface polysaccharides, indicating that the HU-regulon may be central to the switch this organism makes from life as a benign commensal to that of a virulent pathogen.
Another key area of interest in the Davey lab is identification of novel mechanisms of extracellular interspecies (or interkingdom) signaling. There are many undiscovered mechanisms that are the foundation for signal generation and response within bacterial communities. It has been established that DNA is an essential part of the extracellular biofilm matrix of many biofilms. This molecule (eDNA) or certain proteins associated with eDNA, such as HU proteins, may provide a mechanism that relays growth conditions throughout the microbial community. Another potential form of communication is secretion of enzymes that remove key substrates that activate other bacterial species or host cells. Identifying such mechanisms will provide prime targets for the development of therapies to disrupt the formation or function of bacterial populations or microbial communities. The Davey lab is currently investigating this line of study; specifically we are investigating the affect of bacterial arginine deiminases (enzymes that convert L-arginine to citrulline and ammonia) and the release of the amino acid L-arginine on P. gingivalis biofilm formation and pathogenesis.
Selected Peer-Reviewed Publications
- Davey ME, O’Toole GA. (2000) Microbial Biofilms: From Ecology to Molecular Genetics. Microbiol. Mol. Biol. Rev. 64(4):847-867. PMCID: PMC99016
- Davey ME, de Bruijn FJ. (2000) A homologue of the tryptophan-rich sensory protein TspO and FixL regulate a novel nutrient deprivation-induced Sinorhizobium meliloti locus. Appl. Environ. Microbiol. 66(12):5353-5359. PMCID: PMC92468
- Davey ME, Caiazza NC, O’Toole GA. (2003) Rhamnolipid surfactant production affects biofilm architecture in Pseudomonas aeruginosa PAO1. J. Bacteriol. 185(3):1027-1036. PMCID: PMC142794
- Davey, ME, Duncan MJ. (2006) Enhanced biofilm formation and loss of capsule synthesis: Deletion of a putative glycosyltransferase in Porphyromonas gingivalis. J. Bacteriol. 188(15):5510-5523. PMCID:PMC1540017
- Davey ME, Costerton JW. (2006) Molecular genetics analyses of biofilm formation in oral pathogens. Periodontol. 2000 42(1):13-26.
- Davey ME. (2006) Techniques for the growth of Porphyromonas gingivalis biofilms. Periodontol. 2000 42(1): 27-35.
- Davey ME. (2008) Tracking the dynamic interactions during plaque formationÑ. Guest Commentary. J. Bacteriol. 190(24):7869-7870. PMCID: PMC2593234
- Arndt A, Davey ME. (2009) Porphyromonas gingivalis: surface polysaccharides as virulence determinants. In: Sasano T, Suzuki O. (eds).1st Tohoku-Forsyth Symposium, Boston, MA, March 10-11, 2009. Interface Oral Health Science 2009, pp. 382-387.
- Christopher AB, Arndt A, Cugini C, Davey ME. (2010) A streptococcal effector protein that inhibits Porphyromonas gingivalis biofilm development. Microbiology 156(Pt.11):3469-3477. PMID: 20705665
- Alberti-Segui C, Arndt A, Cugini C, Priyadarshini R, Davey ME. (2010) HU protein: Transcription of surface polysaccharide synthesis genes in Porphyromonas gingivalis. J. Bacteriol. 192(23):6217-6229. PMCID: PMC2981211
- Priyadarshini R, Cugini C, Arndt A, Chen T, Tjokro NO, Goodman SD, Davey ME (2012) The nucleoid-associated protein HU-beta affects global gene expression in Porphyromonas gingivalis. Microbiology; 159:219 – 229. PMCID: PMC3709559
- Cugini C, Stephens D N, Nguyen D., Kantarci A, Davey, ME. (2012) Arginine deiminase inhibits Porphyromonas gingivalis surface attachment. Microbiology; 159:275 – 285. PMCID: PMC3709564
- Cugini C, Klepac-Ceraj V, Rackaityte E, Riggs JE, Davey ME. (2013) Porphyromonas gingivalis: keeping the pathos out of the biont. J. Oral Microbiol. 5:19804. PMCID: PMC3617648
- Tjokro NO, Rocco CJ, Priyadarshini R,Davey ME,Goodman SD (2014)A biochemical analysis of the interaction of Porphyromonas gingivalis HU PG0121 protein with DNA. PLoS One.Mar 28;9(3):e93266. PMCID: PMC3969353