19 May Dental Caries: New Approach Breaks Down Harmful Biofilm

MedicalResearch.com Interview with:

Dr. Hwang

Geelsu Hwang, Ph.D.
Assistant Professor
Department of Preventive and Restorative Sciences
Center for Innovation and Precision Dentistry (CiPD)
School of Dental Medicine
University of Pennsylvania 

MedicalResearch.com: What is the background for this study? What is the significance of this oral biofilm? 

Response: Dental caries is one of the most common and costly biofilm-dependent diseases that afflict children and adults worldwide. Particularly, Early Childhood Caries (ECC) is a hyper-virulent type of chronic tooth decay that most frequently afflicts underprivileged preschool children. The onset and progression of carious lesions in ECC are rapid and aggressive, causing rampant destruction of the smooth surfaces of teeth.

ECC is painful and often requires surgical procedure under general anesthesia, while current treatment modalities are inefficient and recurrence of ECC is common. Notably, interactions between a fungus, Candida albicans, and a bacterium, Streptococcus mutans, have been known to play important roles in the pathogenesis of dental caries.

Thus, we attempted to strategically develop a targeted measure to effectively prevent cross-kingdom interactions and subsequent biofilm development.

MedicalResearch.com: What are the main findings?

Response: Bolstered by our previous identification of the interkingdom receptor-ligand binding interaction, we employed mannan-degrading enzymes to disrupt S. mutans-C. albicans interactions by reducing the number of binding sites available to form a mature cross-kingdom biofilm. We found that our enzymatic approach significantly diminished the cross-kingdom biofilm development and its virulence by reducing total biofilm biomass, undermining the mechanical stability of biofilms, alleviating the acidic environment induced by the cross-kingdom biofilms, and reducing demineralization of the tooth enamel surface. Notably, this therapy is devoid of microbiocidal activity while showing no cytotoxicity against human gingival keratinocytes, enabling this as a preventive measure for long-term use.

MedicalResearch.com: What should readers take away from your report?

Response: In the era of antimicrobial resistance, we may need novel nonbiocidal, precise therapeutic measures to address microbially induced infectious diseases. We aimed to targeting and intervening in the interkingdom receptor-ligand binding interactions that minimize off-target effects such as disrupting ecological microbiota, inducing the prevalence of drug resistance, and harming healthy tissues.

MedicalResearch.com: What recommendations do you have for future research as a result of this work?

Response: Target specificity and retention of antibiofilm agents, as well as their penetration behaviors into the biofilm, may determine the fate of the antibiofilm strategy.

Thus, enhanced retention and penetration of our enzymes may further improve the efficacy of this approach. Future studies will assess the possibility of using carriers to improve enzyme delivery. In vivo studies may also provide further insights into this additional therapeutic effect. 

Any disclosures?

I’m an inventor on a patent application (63/174,707) submitted by the University of Pennsylvania that covers enzymatic approach targeting bacterial fungal interaction. 

Citation:

H. E. Kim, A. Dhall, Y. Liu, M. Bawazir, H. Koo, G. Hwang. Intervening in Symbiotic Cross-Kingdom Biofilm Interactions: a Binding Mechanism-Based Nonmicrobicidal Approach. mBio, 2021; 12 (3) DOI: 10.1128/mBio.00651-21

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Last Updated on May 22, 2021 by Marie Benz MD FAAD