FR-31564, a new phosphonic acid antibiotic: bacterial resistance and membrane permeability

Abstract

Mutants which acquired resistance to FR-31564 were also resistant to fosfomycin and vice versa. Some exceptions to cross-resistance were found among clinical isolates of certain species. FR-31564 was found to be incorporated into bacterial cells more efficiently than fosfomycin although the extent of incorporation varied among species. In particular, the uptake rate of FR-31564 by a strain of Pseudomonas aeruginosa was ten times that of fosfomycin. The uptake rate of FR-31564 by both FR-31564- and fosfomycin-resistant mutants was less than one-tenth of that by the parent strain. FR-31564 was scarcely inactivated in the culture broths of FR-31564-resistant strains. All of the FR-31564-resistant mutants of P. aeruginosa came under the classification of strains lacking an L-alpha-glycerophosphate transport system.