Skip to Main Content
Text size: SmallMediumLargeExtra-Large

Something Old, Something New

May 13, 2011

Scardovia wiggsiae coloniesSeveral years ago, the American microbiologist Carl Woese reflected on 20th century biology and offered a word of warning.   Woese wrote that reductionism, the predominant intellectual vehicle of the last century, “had hit the wall of biocomplexity.”  He explained that life, in all its diversity, is too dynamic to reduce to one big engineering project that drills down through genes, proteins, and sugars to find the one presumed disease-causing link in the system.

“Knowing the parts of isolated entities is not enough,” Woese stated.  “A musical metaphor expresses it best:  molecular biology could read notes in the score, but it couldn’t hear the music.”

An example of Woese’s whole-is-greater-than-the-individual-parts warning applies to the study of early childhood caries, or tooth decay.  During most of the 20th century, researchers spent untold hours narrowing down the few presumed caries-causing species in dental plaque.  The consensus was the primary culprit in children and also adults, had to be the oral bacterium Streptococus mutans.  Eliminate S. mutans from the mouth, and the caries rates in young children will drop accordingly.

But biocomplexity soon intervened.  Scientists discovered S. mutans is not the numerically predominant species in sites of decay, nor is the bacterium present in all cases of the disease.  Other species had to play a contributory and possibly causative role.  They needed to find them. 

By the early 1990s, these data fed into the emerging, more ecologically oriented paradigm that the plaque on our teeth is actually more biologically complex than meets the eye.  When brushing, we clear away a living, highly structured, polymicrobial community, or biofilm.   That meant, in addition to identifying a select group of high-value suspects such as S. mutans, researchers had to determine under which oral conditions and community dynamics good biofilms turn bad.  The variables spiked, and that brought additional techniques to the lab to sort out and hopefully simplify the myriad possibilities into a few common scenarios. 

Given their greater appreciation of the biofilm and its complexity, scientists soon found no one molecular or cell-culture technique could produce a comprehensive readout of the microbial conditions in a child’s mouth.  As any good fisherman knows, different bait attracts different fish.  A combination of approaches was needed to produce a comprehensive look, starting with the most fundamental question:  How do the microbes, or microbiota, in the mouths of caries-free and caries-rampant kids differ?  

A team of NIDCR-supported researchers recently published its two-part answer to this question, using a combination of molecular and cell-culture approaches that it backstopped by the bioinformatics of the Human Oral Microbiome Database (HOMD).  The latter is a free online encyclopedic repository of collated biological information on more than 600 oral microbes.  

In the first paper, published in September 2010 on the Caries Research website, the scientists found significant differences in the microbiota of 80 preschool children, about half with severe childhood caries and the rest without decay.  Their data were based specifically on the cloning and amplification of microbial DNA from plaque samples.  This approach indicated that Granulicatella elegans and species within Bifodobacteriaceae seem to be caries-associated pathogens.  So were Neisseria, Veillonella, and some other caries-associated species that do not produce enamel-dissolving acids.  The latter finding suggests these bacteria may have a possible symbiotic or otherwise supportive role in the caries process. 

Interestingly, based on their clonal analysis, the scientists found S. mutans was present infrequently in both groups of children.  However, using PCR assays designed specifically for S. mutans, the bacterium was significantly associated with severe early childhood caries.  They speculated that the discrepancy might be due to the greater sensitivity of PCR assays to pick out low-frequency species, such as S. mutans

“These data are thus consistent with the observation that carious sites may harbor widely diverse bacteria, and S. mutans, while important in disease, may be present only in low proportions at carious sites,” the authors noted. 

In the second paper, published in the April 2011 issue of the Journal of Clinical Microbiology, the scientists upped the investigational ante.  Previous studies on the subject had identified microbes of interest primarily based on phenotype, meaning observable physical or biochemical manifestations.  But looks can be deceiving.  To cast a more comprehensive and informative research net, the scientists started with specially designed, more labor-intensive techniques to grow anaerobic bacteria, the predominant microbes in the oral biofilm and which can be notoriously difficult to culture.  They then employed molecular techniques to pull out signature DNA sequences from the microbes that they could reference in the HOMD database. 

Using this multi-pronged strategy, the scientists compared differences in the microbiota of 82 preschool children, about half with severe childhood caries and the rest without decay.  They again found significant differences in the two groups.  The two major bacterial species associated with decay were S.mutans and a recently named organism called Scardovia wiggsiae.  Intriguingly, S. wiggsiae was associated with severe childhood caries in preschoolers without S. mutans.  Previous studies suggested S. wiggsiae might play a role in childhood caries, and the organism now becomes a candidate for further study.

 

  • Kanasi E, Dewhirst FE, Chalmers NI, Kent R Jr, Moore A, Hughes CV, Pradhan N, Loo CY, Tanner AC. Clonal analysis of the microbiota of severe early childhood caries. Caries Res. 2010;44(5):485-97.

 

 

Tanner AC, Mathney JM, Kent RL, Chalmers NI, Hughes CV, Loo CY, Pradhan N, Kanasi E, Hwang J, Dahlan MA, Papadopolou E, Dewhirst FE. Cultivable anaerobic microbiota of severe early childhood caries. J Clin Microbiol. 2011 Apr;49(4):1464-74.

Share This Page

GooglePlusExternal link – please review our disclaimer

LinkedInExternal link – please review our disclaimer

Print

This page last updated: February 26, 2014