1. Academic Validation
  2. Mutanofactin promotes adhesion and biofilm formation of cariogenic Streptococcus mutans

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

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. boqianpy@ust.hk.
  • 6 Department of Chemical and Biomolecular Engineering, University of California, Berkeley, CA, USA. wjzhang@berkeley.edu.
  • 7 Chan Zuckerberg Biohub, San Francisco, CA, USA. wjzhang@berkeley.edu.
  • # Contributed equally.
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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