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Arthur T Knackerbracket has found the following story:

Early childhood caries, a form of severe tooth decay affecting toddlers and preschoolers, can set children up for a lifetime of dental and health problems. The problem can be significant enough that surgery is the only effective way to treat it.

Recently researchers from the University of Pennsylvania School of Dental Medicine discovered that, in many cases, early childhood caries result from dental plaque that contains both bacteria and fungus working together to make the biofilm on the teeth more pathogenic and difficult to remove. Now they have shown that these two types of microorganisms synergize to enhance drug resistance, enabling the fungal cells to avoid being killed by antifungal therapies. Yet simultaneously targeting the matrix produced by the bacteria along with the fungus offers a way around this protection.

"The current antimicrobial modalities for treating early childhood caries have limited efficacy," says Hyun (Michel) Koo, a professor in the Department of Orthodontics and divisions of Pediatric Dentistry & Community Oral Health in Penn's School of Dental Medicine. "Available evidence shows that biofilm-associated diseases are polymicrobial in nature, including a mix of bacterial and fungal species; therefore a treatment aimed at just one type of microorganism may not be effective. I think this work gives us a glimpse into alternative ways to disrupt cross-kingdom biofilm, a combinatorial approach that considers the fungal and bacterial components."

During the last several years, researchers have observed that the dental plaque in children with early childhood caries often contained Candida albicans, a fungal species that normally colonizes mucosal surfaces, in addition to Streptococcus mutans, the bacteria generally associated with tooth decay. Work in Koo's lab demonstrated that an enzyme produced by the bacteria, termed GtfB, can bind to Candida and when sugar is present (a dietary hallmark in childhood caries) a sticky polymeric matrix forms on its cell surface, enabling the fungus to bind to teeth and associate with bacterial counterparts. Once together, these organisms work in concert to increase severity of tooth decay in a rodent model.

Realizing this, Koo, Kim, and colleagues wanted to see whether a two-pronged approach might break apart the synergistic association and effectively treat the biofilm. "Initially, we decided to look into therapies that are clinically used in dentistry to attack or prevent either fungal or bacterial infections," Koo says.

They came up with fluconazole, which is used as an antifungal, and povidone iodide, which is an antiseptic agent with antibacterial properties. Used alone to treat biofilms grown on a tooth-like material in the lab, the drugs had only moderate effects, confirming that monotherapy doesn't work very well against polymicrobial biofilms. But in combination, the results were much more impressive.

[...] Looking ahead, the Penn-led team hopes their findings lead to new strategies for treating bacterial-fungal infections associated with early childhood caries and possibly other polymicrobial diseases. For the researchers' part, they are making use of nanotechnology to develop targeted approaches that can precisely target the matrix and both the fungal and bacterial components of the oral biofilm.

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