 Ph.D. (1984) |
Robert
G. Quivey
Professor of Microbiology & Immunology Primary
Appointment: Center
Affiliation: GEBS Cluster Affiliations: |
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| Contact Information | ||
| University of Rochester School of Medicine and Dentistry 601 Elmwood Ave, Box 611 Rochester, New York 14642 |
Phone: (585) 275-0382 Fax: (585) 276-0190 E-Mail: Robert_Quivey@ urmc.rochester.edu |
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- Research Focus
- Stress-adaptive gene expression in the oral pathogen, Streptococcus mutans
- Research Overview
- Our research work is focused on a bacterium, Streptococcus mutans, which colonizes the human mouth from the time of tooth eruption until death. The persistence of the organism is remarkable and our efforts are directed to learning the biological means by which it chronically infects virtually every person in the developed nations. The infection requires two relatively simple-minded objectives: bind to tooth surfaces and then survive in the mouth. However, the mouth is a fairly inhospitable environment, containing between 400 and 500 competing bacterial species, volumes of saliva that are swallowed, desquamating soft tissue surfaces, and the swallowing of food (and adsorbed bacteria) as a bolus. Irreversible binding of tooth surfaces occurs by the action of extracellular enzymes produced by S. mutans, the glucosyltransferases (GTFs). These enzymes catalyze the conversion of sucrose, supplied in our diets, to long-chain, insoluble glucans that serve as the molecular scaffold for the formation of dental plaque. If not removed, physically from teeth, the growing mesh of glucan, food particles, bacteria, and salivary constituents continues to accumulate and forms a biofilm referred to as dental plaque. As plaque builds up, S. mutans becomes protected from the flushing effects of saliva and swallowing. In its protected niche, S. mutans metabolism of sugar results in the formation of organic acids and the rapid acidification of the surrounding milieu. As pH values plummet, several orders of magnitude in just seconds, S. mutans begins its adaptation to life at low pH values, where surrounding bacteria can not compete. Our work is in understanding the mechanisms of low pH adaptation and how it relates to bacterial virulence in biofilms.
- Results from our efforts have shown that S. mutans utilizes a number of discrete mechanisms to survive acidic environments. Interestingly, we’ve found that some of the mechanisms are shared with other streptococcal pathogens, and some are shared with streptococcal and staphylococcal pathogens. For example, we’ve shown that the central acid-protective enzyme, the F-ATPase, is transcriptionally up-regulated (“on”) at low pH, which is characteristic shared with S. pneumoniae (Kuhnert et al., 2004). Our data has also shown that S. mutans must make major alterations to its membrane to survive low pH, requiring the action of an enzyme called FabM, a condition that is apparently shared in Staphylococcus aureus (Fozo and Quivey, 2004). Further evidence from our group has shown that resistance to acid-stress overlaps stress from oxidative agents, such as hydrogen peroxide, and that control of oxygen metabolism by an enzyme called NADH oxidase is mediated, in part, by novel mechanisms unique to S. mutans (Karrupaiah et al., 2005). In all of this work, we have focused on identifying those elements that might be useful targets for therapeutic intervention. Our results have shown that identification of unique regulatory schemes or novel enzyme mechanisms involved in stress responses in S. mutans also have a possible usefulness in other human pathogens. We are pursuing or basic science goals, with the inclusion of translational work. For example, we are exploring the use of metal ions, with knowledge gained from DNA repair studies, to develop new therapies for bacterial infection (Faustoferri et al., 2005). We have also begun the use of transgenic mice to study early infection processes (Culp et al., 2005). And, finally, we are developing new technology, in conjunction with the Optics Institute, to rapidly determine the bacterial composition of clinical biofilm samples (Zhu et al., 2004).
- Recent Publications
- Zhu Q, Quivey RG, Berger AJ "Raman spectroscopic measurement of relative concentrations in mixtures of oral bacteria." Appl Spectrosc. 2007 Nov;61(11):1233-7
- Role of unsaturated fatty acid biosynthesis in virulence of Streptococcus mutans." Infect Immun. 2007 Jan 12;
- Koo H, Seils J, Abranches J, Burne RA, Bowen WH, Quivey RG Jr. "Influence of apigenin on gtf gene expression in Streptococcus mutans UA159." Antimicrob Agents Chemother. 2006 Feb;50(2):542-6.
- Faustoferri, R. C., K. Hahn, K. Weiss, and R. G. Quivey, Jr. 2005. "Smx nuclease is the major, low pH-inducible AP endonuclease in Streptococcus mutans." J. Bacteriol. 2005 187: 2705-2714.
- Culp, D. J., R. G. Quivey, W. H. Bowen, M.A. Fallon, S. K. Pearson, and R. Faustoferri. 2005. "A mouse caries model and evaluation of Aqp5-/- knockout mice." Caries Res. 2005 Nov-Dec;39(6):448-54.
- Chatfield, C.H., H. Koo, and R. G. Quivey, Jr. 2005. "The putative autolysin regulator LytR in Streptococcus mutans plays a role in cell division and is growth-phase regulated." Microbiol. 151: 625-631.
- Kuhnert, W.L., G. Zheng, R. C. Faustoferri, and R. G. Quivey, Jr. 2004. "The F-ATPase operon promoter of Streptococcus mutans is transcriptionally regulated in response to external pH." J. Bacteriol. 186 (24): 8524-8528.
- Zhu, Q., R.G. Quivey, and A. J. Berger. 2004. "Measurement of bacterial concentration fractions in polymicrobial mixtures by Raman microspectroscopy." J. Biomed. Optics, 9 (6): 1182-1186.
- Fozo, E. M., J. K. Kajfasz, R.G. Quivey, Jr. 2004. "Low pH-induced membrane fatty acid alterations in oral bacteria." FEMS Microbiol. Letts.238: 291-295.
- Fozo, E.M. and R. G. Quivey, Jr. 2004. "Shifts in the membrane fatty acid profile of Streptococcus mutans are required for survival in acidic environments." Appl. Environ. Microbiol. 70(2): 929-936.
- Fozo, E.M. and R. G. Quivey, Jr. 2004. "The fabM gene product of Streptococcus mutans is responsible for the synthesis of mono-unsaturated fatty acids and is necessary for low pH survival." J. Bacteriol., 186: 4152-4158.
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