6Y4F

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

(2020) PLoS Pathog 16: e1008707-e1008707

• PubMed: 32780778 Search on PubMedSearch on PubMed Central
• DOI: https://doi.org/10.1371/journal.ppat.1008707
• Primary Citation of Related Structures:  
  6Y4E, 6Y4F


• PubMed Abstract: 
  

  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.

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Organizational Affiliation: 

Department of Cell and Molecular Biology, Uppsala University, Biomedical Center, Uppsala, Sweden.