Mutanofactin promotes adhesion and biofilm formation of cariogenic Streptococcus mutans

  • Nat Chem Biol. 2021 May;17(5):576-584. doi: 10.1038/s41589-021-00745-2.
Zhong-Rui Li  1 ,  Jin Sun   #  2 ,  Yongle Du   #  1 ,  Aifei Pan  1  3 ,  Lin Zeng  4 ,  Roya Maboudian  1 ,  Robert A Burne  4 ,  Pei-Yuan Qian  5 ,  Wenjun Zhang  6  7
Affiliations
  • 1. Department of Chemical and Biomolecular Engineering, University of California, Berkeley, CA, USA.
  • 2. Department of Ocean Science and Hong Kong Branch of the Southern Marine Science and Engineering Guangdong Laboratory (Guangzhou), The Hong Kong University of Science and Technology, Hong Kong, China.
  • 3. State Key Laboratory for Manufacturing Systems Engineering, Xi'an Jiaotong University, Xi'an, China.
  • 4. Department of Oral Biology, College of Dentistry, University of Florida, Gainesville, FL, USA.
  • 5. Department of Ocean Science and Hong Kong Branch of the Southern Marine Science and Engineering Guangdong Laboratory (Guangzhou), The Hong Kong University of Science and Technology, Hong Kong, China. [email protected].
  • 6. Department of Chemical and Biomolecular Engineering, University of California, Berkeley, CA, USA. [email protected].
  • 7. Chan Zuckerberg Biohub, San Francisco, CA, USA. [email protected].
  • # Contributed equally.
PMID: 33664521 DOI: 10.1038/s41589-021-00745-2
Abstract

Cariogenic Streptococcus mutans is known as a predominant etiological agent of dental caries due to its exceptional capacity to form biofilms. From strains of S. mutans isolated from dental plaque, we discovered, in the present study, a polyketide/nonribosomal peptide biosynthetic gene cluster, muf, which directly correlates with a strong biofilm-forming capability. We then identified the muf-associated bioactive product, mutanofactin-697, which contains a new molecular scaffold, along with its biosynthetic logic. Further mode-of-action studies revealed that mutanofactin-697 binds to S. mutans cells and also extracellular DNA, increases Bacterial hydrophobicity, and promotes Bacterial adhesion and subsequent biofilm formation. Our findings provided an example of a microbial secondary metabolite promoting biofilm formation via a physicochemical approach, highlighting the importance of secondary metabolism in mediating critical processes related to the development of dental caries.

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