Biologists have discovered that caries-causing microbes roll on the teeth on fungi

(ORDO NEWS) — The development of caries depends not only on heredity and nutrition, but also on the microbiota of the oral cavity.

Microbiologists and dentists from the US, Germany and Switzerland have studied the interaction of the common culprits of early childhood caries – the fungus Candida albicans and the bacteria Streptococcus mutans.

The experiment, published in Proceedings of the National Academy of Sciences, showed that bacterial and fungal cells form stable conglomerates in saliva.

At the initial stages of tooth colonization, the pseudomycelium of the fungus “walks” with hyphae along the substrate, carrying bacterial cells on itself.

Such an unusual type of movement increases the rate of colonization by a factor of three, and the rate of development of caries by a factor of two.

The human mucosal microbiome is organized in the form of biofilms communities within which there is a complex system of signal exchange and horizontal gene transfer between representatives of different species and kingdoms.

The movement of the bacterium Streptococcus mutans on the pseudomycelium of the fungus Candida albicans.

The oral cavity and the surface of the teeth are no exception in this regard. The aggressiveness of caries may depend on the success of the interaction of microbes with each other.

In recent years, there has been growing evidence that not only acid-producing bacteria, but also fungi of the genus Candida contribute to the development of inflammatory diseases of the oral mucosa and the occurrence of caries (primarily in children).

And this despite the fact that Candida itself does not destroy teeth. The details of the interaction between fungi and bacteria in the human oral cavity are still poorly understood.

Microbiologists and dentists from the University of Pennsylvania, in collaboration with scientists from several American, German and Swiss universities, led by Kurt Drescher (Knut Drescher) and Hyun Koo (Hyun Koo) studied the formation and functioning of a biofilm in saliva in children.

To begin with, they studied saliva samples from thirty children with early childhood caries and fourteen healthy children.

Microscopy showed that during caries, bacteria form communities with pseudomycelium of fungi, and in healthy children in saliva there were only predominantly single cells of microorganisms.

The conglomerates consisted of Streptococcus mutans bacteria and Candida albicans fungi, held together by polysaccharides, which are responsible for the formation of bacteria.

In the center of such a conglomerate are bacterial and fungal cells, on the periphery – fungal.

Biologists have discovered that caries causing microbes roll on the teeth on fungi 2
Organization of the cell community of candida and streptococci in early childhood caries

The authors recreated caries ex vivo using a hydroxyapatite substrate (simulating the surface of a tooth) and sterilized saliva, to which microorganisms were added, and obtained the same microbial communities.

Additional experiments have shown that if you take a fungus of a genetic line that does not form hyphae, or replace S. mutans with another human oral streptococcus (S. gordonii), then multicellular conglomerates do not arise.

The blockade of streptococcal enzymes responsible for the synthesis of the glycan extracellular matrix, as well as the addition of glycosidases to saliva, had the same effect (we talked about the experiment with glycosidases from the same research group: then the enzymes slowed down the development of caries in humans).

The liquid flow easily washed away pure cultures of streptococci and Candida from the surface of the substrate, and mixed communities were quite resistant to mechanical stress.

Moreover, the microorganisms in the conglomerates were 2-4 orders of magnitude less sensitive to the antiseptic chlorhexidine and the antifungal drug nystatin than the same microbes in the form of pure cultures.

Biologists have discovered that caries causing microbes roll on the teeth on fungi 1
Stability of microbial communities (pure cultures or interspecies) under the action of fluid flow (left) and antimicrobials (right)

Observation of the initial stage of biofilm formation made it possible to discover the way streptococci migrate, which the authors called “hitchhiking”. After attaching to the tooth surface, the community chooses the direction of growth.

With the onset of growth, the pseudomycelium of the fungus lifts the bacterial cells above the surface and carries the streptococci, “walking” the hyphae of the fungus along the surface of the substrate.

The migration rate at the initial stage of biofilm formation reached about 15 micrometers per hour (this is about 10-15 diameters of streptococcus cells that do not have movement organelles).

Thanks to Candida, streptococci took up three times more substrate surface than in the pure culture control experiment.

The rate of invasion deep into the matrix in the biofilm was twice as high as in the culture of streptococci, and amounted to 40 micrometers in about three days.

Migration of streptococci (green) on the surface of Candida fungi.

According to the authors, understanding the interaction of different components of the microbiome will improve our understanding of the pathogenesis and treatment of many infectious diseases.

And although the molecular background and significance of the phenomenon for adult caries (in which streptococcus does not play a leading role in dental diseases) is still unknown, further study of the oral microbiome may bring us closer to the cure for caries and move us away from the drill.

But not only microbiologists are doing their bit in the fight against caries: the factors influencing its occurrence are well understood through comparison of archaeological finds, the study of the human diet, and the analysis of the incidence of twins.

And the study of the molecular mechanisms of dentin and pulp regeneration has even made it possible to cure caries, though so far only in animals.

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