Structure and Dynamics of FosA-Mediated Fosfomycin Resistance in Klebsiella pneumoniae and Escherichia coli.

ABSTRACT: Fosfomycin exhibits broad-spectrum antibacterial activity and is being reevaluated for the treatment of extensively drug-resistant pathogens. Its activity in Gram-negative organisms, however, can be compromised by expression of FosA, a metal-dependent transferase that catalyzes the conjugation of glutathione to fosfomycin, rendering the antibiotic inactive. In this study, we solved the crystal structures of two of the most clinically relevant FosA enzymes: plasmid-encoded FosA3 from Escherichia coli and chromosomally encoded FosA from Klebsiella pneumoniae (FosA^KP). The structure, molecular dynamics, catalytic activity, and fosfomycin resistance of FosA3 and FosA^KP were also compared to those of FosA from Pseudomonas aeruginosa (FosA^PA)

SUBMITTER: Klontz EH 

PROVIDER: S-EPMC5655077 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature