Abstracts of Current Research
Unlike other infectious diseases, dental diseases are not inflicted by one specific pathogen but evolve from multispecies biofilms attached to the oral surfaces.
The oral biofilm is a complex (approximately 700 bacterial species) structured community which is dependent upon microbial communication. Our research concentrates on factors and phases involved in the transition from a commensial oral biofilm to a virulent one involved in oral diseases.
1. Fusobacterium nucleatum and coaggregation:
A long anaerobic rod, F. nucleatum are unique in their diverse attachment ability which bridges between late dental bacterial colonizers and early dental colonizers equipped for adhering to oral surfaces in a process termed coaggregation . Late colonizers are the bacteria associated with periodontal disease and therefore have great clinical significance. Coaggregation is also hypothesized to create juxtapositioning that enhances interspecies communication among oral bacteria . F. nucleatum, is also the oral pathogen most frequently isolated from systemic infections.
Lack of genetic system for gene manipulation in F. nucleatum has hampered study of this organism. To test the importance of the F. nucleatum bridging activity to the development of the dental plaque, we have isolated plasmids from F. nucleatum isolates, and have developed shuttle vectors for use in fusobacteria. We are now working on creating genetic tools for random gene inactivation mutagenesis in fusobacteria. These tools, which are currently unavailable, will enable the identification of the coaggregation-mediating adhesins. Identification of coaggregation-mediating adhesins is expected to lead to the development of novel approaches for prevention and treatment of oral diseases.
Periodontitis has been recently recognized as a risk factor for preterm labor and F. nucleatum , is emerging as the bacteria closely associated with preterm deliveries. Attachment of F. nucleatum to host cells is hypothesized to be essential for the fusobacterial ability to invade the fetoplacental unit and induce preterm birth. We are now developing genetic tools and biochemical approaches to identify the F. nucleatum adhesins involved in attachment to host cells and in the fusobacterial virulence associated with preterm deliveries.
2. Host defense peptides are effector molecules of the innate immune system that possess a broad spectrum of antimicrobial activity. We have explored the effectiveness of various chemically synthesized antimicrobial peptides against common oral pathogens. Some oral pathogens were found to resist host defense peptides by degrading them.
LL-37 is a human antimicrobial peptide suggested to play a major role in defense against periodontal pathogens. We have recently observed that saliva specifically protects LL-37 from degradation by periodontal pathogens. We are now working towards the identification of this host defense peptide protective salivary factor.
3 . Salivary diagnostics and salivary immunity in oral diseases: It is apparent that saliva, being readily accessible (noninvasive), holds great potential as a medium for screening large populations for the occurrence or susceptibility to disease. For this purpose and in collaboration with Dr. Stella Chaushu from the Orthodontics department, we have adapted and are utilizing high-throughput screening methods for screening large numbers of saliva samples for the occurrence of large numbers of pathogens, and for quantifying the salivary immunity in many saliva samples to multiple antigens. High-throughput salivary screening and diagnostic capabilities are expected to improve clinical treatment by monitoring its progress.
- Bachrach, G., H. Altman, P. E. Kolenbrander, N. I. Chalmers, M. Gabai-Gutner, A. Mor, M. Friedman and D. Steinberg (2008). "Resistance of Porphyromonas gingivalis ATCC 33277 to Direct Killing by Antimicrobial Peptides Is Protease Independent." Antimicrob Agents Chemother 52 (2): 638-42.
- Bachrach, G., Z. Muster, I. Raz, G. Chaushu, A. Stabholz, G. Nussbaum, M. Gutner and S. Chaushu (2008). "Assessing the levels of immunoglobulins in the saliva of diabetic individuals with periodontitis using checkerboard immunodetection." Oral Dis 14 (1): 51-9.
- Chaushu, S., G. Chaushu, M. Zigmond, E. Yefenof, A. Stabholz, J. Shapira, J. Merrick and G. Bachrach (2007). "Age-dependent deficiency in saliva and salivary antibodies secretion in Down's syndrome." Arch Oral Biol 52 (11): 1088-96.
- Altman, H., D. Steinberg, Y. Porat, A. Mor, D. Fridman, M. Friedman and G. Bachrach (2006). "In vitro assessment of antimicrobial peptides as potential agents against several oral bacteria." J Antimicrob Chemother 58 (1): 198-201.
- Bachrach, G., G. Chaushu, M. Zigmond, E. Yefenof, A. Stabholz, J. Shapira, J. Merrick and S. Chaushu (2006). "Salivary LL-37 secretion in individuals with Down syndrome is normal." J Dent Res 85 (10): 933-6.
- Bachrach, G., M. Friedman, G. Gilinski and D. Steinberg (2006). "Soluble sustained release gene delivery system." J Biomed Mater Res A 77 (4): 811-4.
- Burns, E., G. Bachrach, L. Shapira and G. Nussbaum (2006). "Cutting Edge: TLR2 is required for the innate response to Porphyromonas gingivalis : activation leads to bacterial persistence and TLR2 deficiency attenuates induced alveolar bone resorption." J Immunol 177 (12): 8296-300.
- Zigmond, M., A. Stabholz, J. Shapira, G. Bachrach, G. Chaushu, A. Becker, E. Yefenof, J. Merrick and S. Chaushu (2006). "The outcome of a preventive dental care programme on the prevalence of localized aggressive periodontitis in Down's syndrome individuals." J Intellect Disabil Res 50 (Pt 7): 492-500.
- Bachrach, G., C. Ianculovici, R. Naor and E. I. Weiss (2005). "Fluorescence based measurements of Fusobacterium nucleatum coaggregation and of fusobacterial attachment to mammalian cells." FEMS Microbiol Lett 248 (2): 235-40.
- Bachrach, G., S. K. Haake, A. Glick, R. Hazan, R. Naor, R. N. Andersen and P. E. Kolenbrander (2004). "Characterization of the novel Fusobacterium nucleatum plasmid pKH9 and evidence of an addiction system." Appl Environ Microbiol 70 (12): 6957-62.
- Bachrach, G., G. Rosen, M. Bellalou, R. Naor and M. N. Sela (2004). "Identification of a Fusobacterium nucleatum 65 kDa serine protease." Oral Microbiol Immunol 19 (3): 155-9.
- Rozen, R., G. Bachrach and D. Steinberg (2004). "Effect of carbohydrates on fructosyltransferase expression and distribution in Streptococcus mutans GS-5 biofilms." Carbohydr Res 339 (18): 2883-8.
- Rozen, R., D. Steinberg and G. Bachrach (2004). " Streptococcus mutans fructosyltransferase interactions with glucans." FEMS Microbiol Lett 232 (1): 39-43.
- Bachrach, G., M. Leizerovici-Zigmond, A. Zlotkin, R. Naor and D. Steinberg (2003). "Bacteriophage isolation from human saliva." Lett Appl Microbiol 36 (1): 50-3.
- Rahav, G., E. Pinco, G. Bachrach and H. Bercovier (2003). "Molecular epidemiology of asymptomatic bacteriuria in the elderly." Age Ageing 32 (6): 670-3.
Rozen, R., G. Bachrach, B. Zaks, M. Bronshteyn, I. Gedalia and D. Steinberg (2003). "Effect of chlorhexidine on molecular weight distribution of fructans produced by fructosyltransferase in solution and immobilized on surface." Carbohydr Res 338 (6): 571-5.
- Kolenbrander, P. E., N. S. Jakubovics, N. I. Chalmers and G. Bachrach (2007). Coaggregation and distance-critical communication. Virulence Mechanisms of Bacterial Pathogens . K. A. Brogden, F. C. Minion, N. Cornicket al. Washington , D.C., American Society for Microbiology Press : 89-100.
- Rickard, A. H., G. Bachrach and D. G. Davies (2008). Cell-cell Communication in Oral Microbial Communities. Molecular Oral Microbiology . A. H. Rogers. Portland, OR, Caister Academic Press : 83-104.