Mechanisms of acquired penicillin-resistance in Streptomyces cacaoi. Role of penicillin-binding proteins in penicillin resistant mutants.
Several mutants isolated after N-methyl-N'-nitro-N-nitrosoguanidine mutagenesis of Streptomyces cacaoi strain KCCS-0352, were resistant to benzylpenicillin ranging in concentration from 1,000 to 5,000 micrograms/ml (4- to 20-fold more resistant than the parent). These mutants also acquired resistance to mecillinam, cephamycin C and methicillin. The affinity for beta-lactams of penicillin-binding proteins (including PBP-2--a possible lethal target of beta-lactams in Streptomyces cacaoi) in the mutants decreased. Addition of Triton X-100 or ethylenediaminetetraacetic acid, but not toluene, reduced the minimum inhibitory concentration of beta-lactams. In vitro accessibility of [14C]benzylpenicillin to whole cells and membrane fractions was lower in the mutants than in the parent. The binding of beta-lactams to penicillin-binding proteins in both the parent and mutants was increased by pretreatment with Triton X-100 or ethylenediaminetetraacetic acid. The results of this study of penicillin-binding suggest that penicillin-binding proteins play a major role in "acquired" resistance as well as "intrinsic" resistance.
D001426:Bacterial Proteins; D002352:Carrier Proteins / Q000502:physiology*; D055598:Chemical Phenomena; D002621:Chemistry; D004347:Drug Interactions; D004492:Edetic Acid / Q000494:pharmacology; D006602:Hexosyltransferases; D002267:Muramoylpentapeptide Carboxypeptidase; D009154:Mutation; D017830:Octoxynol; D010400:Penicillin G / Q000494:pharmacology; D010403:Penicillin Resistance; D046915:Penicillin-Binding Proteins; D010458:Peptidyl Transferases; D011092:Polyethylene Glycols / Q000494:pharmacology; D013302:Streptomyces / Q000187:drug effects* / Q000378:metabolism
D001426:Bacterial Proteins; D002352:Carrier Proteins; D046915:Penicillin-Binding Proteins; D011092:Polyethylene Glycols; D017830:Octoxynol; D004492:Edetic Acid; D010458:Peptidyl Transferases; D006602:Hexosyltransferases; D002267:Muramoylpentapeptide Carboxypeptidase; D010400:Penicillin G