Jonathon Baker, PhD, joined the Department of Genomic Medicine at JCVI in 2018. Dr. Baker’s research is focused primarily on the disease, dental caries, commonly referred to as “cavities” or “tooth decay.” Dental caries is the most common chronic infectious disease, globally, and will afflict roughly 90% of Americans at some point in their lives. This extraordinary rate of infection, combined with high cost of treatment, translates to a massive global economic burden, approaching US$300 billion, annually.

Historically, infection by the oral bacterium Streptococcus mutans was thought to be the primary cause of dental caries. S. mutans causes disease by forming biofilms (dental plaque), firmly attached to the tooth surface, and generating large amounts of organic acids—by-products of its metabolism of the sugars it comes into contact with, thanks to the human diet. These acids destroy the protective enamel coating on the tooth surface, and will lead to loss of the tooth if the disease process is unchecked. In the era of next-generation sequencing, caries is increasingly recognized as a polymicrobial disease, caused by an ecological catastrophe in the plaque environment, rather than infection by a single species. Thus, the role of S. mutans as the keystone pathogen in caries progression has been called into question. Dr. Baker’s research seeks to understand how S. mutans, and its bacterial neighbors in dental plaque, influence and interact with one another, and how these relationships affect the ability of these communities of bacteria to cause disease.

In addition, since tooth enamel is the hardest surface in the human body, it is remarkable that S. mutans and other caries-causing bacteria are able to survive in conditions that are so acidic that they significantly demineralize enamel. One of the mechanisms employed by S. mutans to survive acid stress is increasing the proportion of unsaturated fatty acids (UFAs) in its cell membrane which occurs via the FabM isomerase enzyme. Although this adaptation is required for acid tolerance and virulence, it is not known how this shift is activated or controlled, or how the UFAs are protective. Dr. Baker’s research seeks to answer these questions, as well as determine how widespread this behavior is, since preliminary data indicates several other oral bacteria increase membrane UFAs in response to acid stress. The results obtained from this investigation are likely to open the door to development of novel anti-caries therapeutics.

Originally from Rochester, NY, Dr. Baker has a PhD in microbiology & immunology from the University of Rochester School of Medicine & Dentistry and a BS in biology from SUNY Geneseo. Prior to joining the team at JCVI, Dr. Baker conducted research in the Department of Oral Biology at the UCLA School of Dentistry and in the Vaccine Research and Early Development group at Pfizer, Inc. in Pearl River, NY.

Research Priorities

Investigating membrane alterations as a mechanism of acid tolerance in cavity-causing bacteria
  • Determine what bacteria in the oral microbiota modify their membranes and/or cell walls in response to environmental acidification
  • Determine how these membrane and cell wall alterations are effective at protecting disease-causing bacteria from acid
  • Develop anti-caries therapeutics that disrupt caries-causing bacteria from altering their cell envelope and therefore prevent further acid damage to the tooth enamel
Identifying and characterizing interspecies interactions between S. mutans and other dental plaque bacteria that affect virulence of the community
  • Identifying contributing species
  • Discovering the mechanisms of interaction/signaling
  • Applying novel information to better understand how the plaque community interacts with the host and causes disease

Publications

Composite Long- and Short-Read Sequencing Delivers a Complete Genome Sequence of B04Sm5, a Reutericyclin- and Mutanocyclin-Producing Strain of Streptococcus mutans.
Microbiology resource announcements. 2020-11-19; 9.47:
PMID: 33214302
Streptococcus mutans SpxA2 relays the signal of cell envelope stress from LiaR to effectors that maintain cell wall and membrane homeostasis.
Molecular oral microbiology. 2020-06-01; 35.3: 118-128.
PMID: 32043713
Klebsiella and Providencia emerge as lone survivors following long-term starvation of oral microbiota.
Proceedings of the National Academy of Sciences of the United States of America. 2019-04-23; 116.17: 8499-8504.
PMID: 30975748
Identification of the Bacterial Biosynthetic Gene Clusters of the Oral Microbiome Illuminates the Unexplored Social Language of Bacteria during Health and Disease.
mBio. 2019-04-16; 10.2:
PMID: 30992349
Exploiting the Oral Microbiome to Prevent Tooth Decay: Has Evolution Already Provided the Best Tools?
Frontiers in microbiology. 2019-01-11; 9.3323.
PMID: 30687294
Ecology of the Oral Microbiome: Beyond Bacteria.
Trends in microbiology. 2017-05-01; 25.5: 362-374.
PMID: 28089325
Acid-adaptive mechanisms of Streptococcus mutans-the more we know, the more we don't.
Molecular oral microbiology. 2017-04-01; 32.2: 107-117.
PMID: 27115703
A Modified Chromogenic Assay for Determination of the Ratio of Free Intracellular NAD+/NADH in Streptococcus mutans.
Bio-protocol. 2016-08-20; 6.16:
PMID: 28516115
Transcriptional profile of glucose-shocked and acid-adapted strains of Streptococcus mutans.
Molecular oral microbiology. 2015-12-01; 30.6: 496-517.
PMID: 26042838
Loss of NADH Oxidase Activity in Streptococcus mutans Leads to Rex-Mediated Overcompensation in NAD+ Regeneration by Lactate Dehydrogenase.
Journal of bacteriology. 2015-12-01; 197.23: 3645-57.
PMID: 26350138
Streptococcus mutans NADH oxidase lies at the intersection of overlapping regulons controlled by oxygen and NAD+ levels.
Journal of bacteriology. 2014-06-01; 196.12: 2166-77.
PMID: 24682329
Development and comparison of a quantitative TaqMan-MGB real-time PCR assay to three other methods of quantifying vaccinia virions.
Journal of virological methods. 2014-02-01; 196.126-32.
PMID: 24211297
Host factor SAMHD1 restricts DNA viruses in non-dividing myeloid cells.
PLoS pathogens. 2013-01-01; 9.6: e1003481.
PMID: 23825958
When Starved, Dangerous Oral Bacteria Hang On