Affordable Access

deepdyve-link
Publisher Website

Cariogenic Streptococcus mutans Produces Tetramic Acid Strain-Specific Antibiotics That Impair Commensal Colonization.

Authors
  • Tang, Xiaoyu1, 2
  • Kudo, Yuta2
  • Baker, Jonathon L1
  • LaBonte, Sandra1, 3
  • Jordan, Peter A2
  • McKinnie, Shaun M K2
  • Guo, Jian4
  • Huan, Tao4
  • Moore, Bradley S2, 5
  • Edlund, Anna1
  • 1 Genomic Medicine Group, J. Craig Venter Institute, 4120 Capricorn Lane, La Jolla, California 92037, United States. , (United States)
  • 2 Scripps Institution of Oceanography, University of California San Diego, 9500 Gilman Drive, La Jolla, California 92093-0204, United States. , (United States)
  • 3 Department of Biochemistry and Biophysics, Texas A&M University and Texas AgriLife Research, College Station, Texas 77843-2128, United States. , (United States)
  • 4 Department of Chemistry, University of British Columbia, Vancouver Campus, 2036 Main Mall, Vancouver, British Columbia V6T 1Z1, Canada. , (Canada)
  • 5 Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California at San Diego, 9500 Gilman Drive, La Jolla, California 92093, United States. , (United States)
Type
Published Article
Journal
ACS Infectious Diseases
Publisher
American Chemical Society
Publication Date
Apr 10, 2020
Volume
6
Issue
4
Pages
563–571
Identifiers
DOI: 10.1021/acsinfecdis.9b00365
PMID: 31906623
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Streptococcus mutans 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 muc, a hybrid polyketide synthase and nonribosomal peptide synthetase (PKS/NRPS) biosynthetic gene cluster (BGC), present in a number of globally distributed S. mutans strains. The natural products synthesized by muc included three N-acyl tetramic acid compounds (reutericyclin and two novel analogues) and an unacylated tetramic acid (mutanocyclin). Furthermore, the enzyme encoded by mucF 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, S. mutans utilized the reutericyclin produced by muc to impair the growth of neighboring oral commensal bacteria. Since S. mutans must be able to out-compete these health-associated organisms to persist in the oral microbiota and cause disease, the competitive advantage conferred by muc suggests that this BGC is likely to be involved in S. mutans ecology and therefore dental plaque dysbiosis and the resulting caries pathogenesis.

Report this publication

Statistics

Seen <100 times