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Hardness of development of drug-resistant bacteria has cross relation with mechanisms of antibacterial activities of antimicrobial agents. When the site of action of certain antibiotic is single enzyme and the enzyme can be converted to tolerant against the antibiotic by change of single amino acid retaining the enzymatic activity, drug-resistant bacteria can emerge easily. On the other hand, if the site of action is complex metabolic reactions, the drug-resistant bacteria would emerge hardly, because multiple mutations are required in this case. So that knowledges of mechanisms of antimicrobial agents are important to prevent the development of drug-resistant bacteria. Antimicrobial agents are classified into several categories, i.e. inhibitors for bacterial cell wall such as beta-lactam drugs, fosfomycin, and vancomycin; inhibitors for protein biosynthesis such as tetracyclibnes, macrolides, aminoglycoside antibiotics; inhibitors for DNA synthesis such as 4-quinolones; inhibitors for RNA synthesis such as rifampicin.

We examined effect of fosfomycin (FOM) on growth of Escherichia coli (E. coli) NIHJ JC-2, multidrug-resistant Pseudomonas aeruginosa (P. aeruginosa) PFS80 and Staphylococcus aureus (S. aureus) Smith. FOM inhibited the growth of these organisms at 0.1 approximately 0.5, 10 approximately 50 or 5 approximately 50 micrograms ml, respectively. In E. coli, FOM clearly lyzed the cells at 0.5 microgram/ml. These 3 bacteria incorporated radiolabeled FOM proportionately to incubation time. Intracellular concentration of FOM was estimated by considering the water content of E. coli cells. The ratio of intracellular to extracellular concentrations of FOM was larger than 1 after 5 approximately 10 min. incubation with FOM and reached about 7 after 40 min. FOM was incorporated actively into P. aeruginosa over extracellular concentration after 40-min. incubation on the basis of the above-mentioned water content. It was suggested that FOM was incorporated actively into various bacterial cells, and inhibited efficiently cell wall peptidoglycan synthesis, thus inhibited bacterial growth or lyzed the bacterial cells.