About the affinity of cefotaxime and its anti isomer for the penicillin-binding proteins.

Recently COSTA and BOTTA" published a study of the interactions with penicillin-binding proteins (PBPs) of Escherichia coli of cefotaxime, its anti isomer and the analogue without the oxime function. They concluded that the differences in antibacterial activities of the compounds was much related to differences in their ability to penetrate the outer cell layers, rather than their affinity for the target PBPs. We have also performed similar work'), but concluded that the difference in antibacterial activities between cefotaxime and its anti isomer is closely related to their affinities for the PBPs. SHIGI et al.') have described a similar study using ceftizoxime and its anti isomer. They have suggested that the difference in antibacterial activity of the two isomers is "likely to be due to difference between the two compounds in their abilities to inhibit peptidoglycan polymerization". SHIGI et al., as in our investigation, employed E. coli DC 0 whereas COSTA and BOTTA used E. coli KN 126. Nevertheless, these two strains, each derived from E. coli K 12 might be expected to behave similarly towards ;9-lactam antibiotics. In fact, the MICs 1.45 and 400 yg/ml found for cefotaxime and its anti isomer respectively using E. coli KN 1261', differ considerably from the values 0.032 and 3.2 hg/ml respectively obtained by us using E. coli DC 0. These are very similar to those found for ceftizoxime and its anti isomer (viz., 0.05 and 1.56 ,ug/ml) by SHIGI et al.'). It should also be noticed that the MIC values obtained by COSTA and BOTTA using cefotaxime seemed unusually high for an E. coli strain". E. coli KN 126 has been used, frequently, by SPRATT for PBPs studies (inter al, ref 5). It was originally described by NAGATA6' and has been derived from E. coli K 12-9829, a strain from the collection of OZEKI". E. coli DC 0, which originated from RICHMOND'' is also named UB 1005. Few hypersensitive mutants have been prepared',') from this strain. The strain DC 2 has been subject to extensive studies, particularly in the field of penetration of ,5-lactam antibiotics in bacteria. E. coli KN 126 and E. coli DC 0 have been found to be sensitive to most of the well-known 9-lactam antibiotics. We suggest that the difference in the conclusions in the two papers'," is most reasonably attributable to a spontaneous mutation, or alteration, probably in the porin system, of COSTA and BOTTA's E. coli KN 126. We still think that for the majority of E. coli strains the difference between the antibacterial activity of cefotaxime and its anti isomer is mostly related to different capacities for binding to the penicillinbinding proteins.