Abstract
Streptococcus mutans is a Gram-positive bacterium that thrives under acidic conditions and is a primary cause of tooth decay (dental caries). To better understand the metabolism of S. mutans on a systematic level, we manually constructed a genome-scale metabolic model of the S. mutans type strain UA159. The model, called iSMU, contains 675 reactions involving 429 metabolites and the products of 493 genes. We validated iSMU by comparing simulations with growth experiments in defined medium. The model simulations matched experimental results for 17 of 18 carbon source utilization assays and 47 of 49 nutrient depletion assays. We also simulated the effects of single gene deletions. The model's predictions agreed with 78.1% and 84.4% of the gene essentiality predictions from two experimental data sets. Our manually curated model is more accurate than S. mutans models generated from automated reconstruction pipelines and more complete than other manually curated models. We used iSMU to generate hypotheses about the S. mutans metabolic network. Subsequent genetic experiments confirmed that (i) S. mutans catabolizes sorbitol via a sorbitol-6-phosphate 2-dehydrogenase (SMU_308) and (ii) the Leloir pathway is required for growth on complex carbohydrates such as raffinose. We believe the iSMU model is an important resource for understanding the metabolism of S. mutans and guiding future experiments.IMPORTANCE Tooth decay is the most prevalent chronic disease in the United States. Decay is caused by the bacterium Streptococcus mutans, an oral pathogen that ferments sugars into tooth-destroying lactic acid. We constructed a complete metabolic model of S. mutans to systematically investigate how the bacterium grows. The model provides a valuable resource for understanding and targeting S. mutans' ability to outcompete other species in the oral microbiome.
Highlights
Streptococcus mutans is a Gram-positive bacterium that thrives under acidic conditions and is a primary cause of tooth decay
We manually reconstructed an in silico metabolic model for S. mutans type strain UA159 (Fig. 1A)
We found that S. mutans UA159 can grow in chemically defined medium (CDM) without either folate or aminobenzoate but is unable to grow in medium lacking both (Fig. 3)
Summary
Streptococcus mutans is a Gram-positive bacterium that thrives under acidic conditions and is a primary cause of tooth decay (dental caries). We believe the iSMU model is an important resource for understanding the metabolism of S. mutans and guiding future experiments. Decay is caused by the bacterium Streptococcus mutans, an oral pathogen that ferments sugars into tooth-destroying lactic acid. We constructed a complete metabolic model of S. mutans to systematically investigate how the bacterium grows. Streptococcus mutans is one of over 600 species of bacteria in the oral microbiome [1] This Gram-positive, lactic acid bacterium thrives in the oral environment in part due to its metabolic flexibility. Previous studies have shown that acid production and tolerance in S. mutans require large changes in gene expression and metabolic pathway utilization [5]. Jijakli and Jensen accompanied by an increased expression of F-ATPases to maintain a higher intracellular pH [7]
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