Open AccessMrpH, a new class of metal-binding adhesin, requires zinc to mediate biofilm formation
Author(s) -
Wangshu Jiang,
Wimal Ubhayasekera,
Michael C. Breed,
Allison N. Norsworthy,
Nina Serr,
Harry L. T. Mobley,
Melanie M. Pearson,
Stefan D. Knight
Publication year - 2020
Publication title -
plos pathogens
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.719
H-Index - 206
eISSN - 1553-7374
pISSN - 1553-7366
DOI - 10.1371/journal.ppat.1008707
Subject(s) - proteus mirabilis , fimbria , biofilm , bacterial adhesin , microbiology and biotechnology , chemistry , zinc , complementation , biology , binding site , mutant , escherichia coli , biochemistry , bacteria , genetics , organic chemistry , gene
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 Zn 2+ 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.