A number of natural product phosphonate substances with antibiotic properties have been identified. Phosphonate natural product antibiotics include fosfomycin which is approved by FDA for the treatment of non-complicated urinary tract infection as well as several pre-clinically investigated substances such as Fosmidomycin (inhibitor isoprenyl synthase), SF-2312 (inhibitor of the glycolytic enzyme enolase, and substances of unknown mode of actions such as alahopcin. Although phosphonates are profoundly cell impermeable, natural product phosphonate antibiotics are effective against a number of organisms, because many bacterial species express glycerol-3-phosphate and glucose-6-phosphate importers, which can be hijaked by phosphonate antibiotics. Fosfomycin resistant bacterial strains frequently have mutations that inactivate these transporters; however, such mutations are not maintained in the absence of antibiotic because of the fitness cost they impose.