MrpH, a new class of metal-binding adhesin, requires zinc to mediate biofilm formation

PLoS Pathog. 2020 Aug 11;16(8):e1008707. doi: 10.1371/journal.ppat.1008707. eCollection 2020 Aug.


Proteus mirabilis, a Gram-negative uropathogen, is a major causative agent in catheter-associated urinary tract infections (CAUTI). Mannose-resistant Proteus-like fimbriae (MR/P) are crucially important for P. mirabilis infectivity and are required for biofilm formation and auto-aggregation, as well as for bladder and kidney colonization. Here, the X-ray crystal structure of the MR/P tip adhesin, MrpH, is reported. The structure has a fold not previously described and contains a transition metal center with Zn2+ coordinated by three conserved histidine residues and a ligand. Using biofilm assays, chelation, metal complementation, and site-directed mutagenesis of the three histidines, we show that an intact metal binding site occupied by zinc is essential for MR/P fimbria-mediated biofilm formation, and furthermore, that P. mirabilis biofilm formation is reversible in a zinc-dependent manner. Zinc is also required for MR/P-dependent agglutination of erythrocytes, and mutation of the metal binding site renders P. mirabilis unfit in a mouse model of UTI. The studies presented here provide important clues as to the mechanism of MR/P-mediated biofilm formation and serve as a starting point for identifying the physiological MR/P fimbrial receptor.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adhesins, Bacterial / chemistry
  • Adhesins, Bacterial / genetics
  • Adhesins, Bacterial / metabolism*
  • Amino Acid Sequence
  • Biofilms*
  • Fimbriae Proteins / chemistry
  • Fimbriae Proteins / genetics
  • Fimbriae Proteins / metabolism*
  • Humans
  • Proteus Infections / metabolism
  • Proteus Infections / microbiology
  • Proteus mirabilis / chemistry
  • Proteus mirabilis / genetics
  • Proteus mirabilis / metabolism*
  • Sequence Alignment
  • Urinary Tract Infections / metabolism
  • Urinary Tract Infections / microbiology*
  • Zinc / chemistry
  • Zinc / metabolism*


  • Adhesins, Bacterial
  • MrpH protein, Proteus mirabilis
  • Fimbriae Proteins
  • Zinc