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Jiang W, Ubhayasekera W, Breed MC, Norsworthy AN, Serr N, Mobley HLT, Pearson MM, Knight SD
PLoS Pathog. 16 (8) e1008707 [2020-08-00; online 2020-08-11]
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.
Protein Science Facility (PSF) [Service]
PubMed 32780778
DOI 10.1371/journal.ppat.1008707
Crossref 10.1371/journal.ppat.1008707
pmc: PMC7444556
pii: PPATHOGENS-D-20-00342