Cariogenic Streptococcus mutans Produces Tetramic Acid Strain-Specific Antibiotics That Impair Commensal Colonization
Tang X, Kudo Y, Baker J, Baker JL, LaBonte S, Jordan P, Jordan PA, McKinnie SMK, McKinnie S, Guo J, Huan T, Moore BS, Edlund A
is a common constituent of dental plaque and a major etiologic agent of dental caries (tooth decay). In this study, we elucidated the biosynthetic pathway encoded by , a hybrid polyketide synthase and nonribosomal peptide synthetase (PKS/NRPS) biosynthetic gene cluster (BGC), present in a number of globally distributed strains. The natural products synthesized by included three -acyl tetramic acid compounds (reutericyclin and two novel analogues) and an unacylated tetramic acid (mutanocyclin). Furthermore, the enzyme encoded by was identified as a novel class of membrane-associated aminoacylases and was responsible for the deacylation of reutericyclin to mutanocyclin. A large number of hypothetical proteins across a broad diversity of bacteria were homologous to MucF, suggesting that this may represent a large family of unexplored acylases. Finally, utilized the reutericyclin produced by to impair the growth of neighboring oral commensal bacteria. Since must be able to out-compete these health-associated organisms to persist in the oral microbiota and cause disease, the competitive advantage conferred by suggests that this BGC is likely to be involved in ecology and therefore dental plaque dysbiosis and the resulting caries pathogenesis.