Penicillinase discovery

Considerable work went into modification of the strain (through the use of X-rays or UV light to induce mutations) and improvements were made in the technology of isolation and purification. However, the mould was much more difficult to handle and would not accept alternative side-chain precursors as did Penicillium chrysogenum hence, it was impossible to prepare semi-synthetic cephalosporins by this route. In addition, the discovery of methicillin with its resistance to penicillinases negated the advantages of cephalosporin C, and for a while it appeared that this new class of antibiotics was doomed. 

Since 1959 relatively few newly discovered microbial metabolites have reached general use in human or veterinary medicine (Table IV) most of the major discoveries (the penicillinase-resistant penicillins, the... 

The penicillinase of the title is the penicillin ) -lactamase (EC S.5.2.6) which hydrolyzes the substituted amide bond in the four-membered ring in penicillin, producing penicilloic add. Bacterial penicillinases show a general group spedlicity in hydrolyzing, as well as the naturally produced penicillins, many synthetic acyl derivatives of 6-aminopenicil-lanic acid, though the rate of destruction depends both on the nature of the acyl side chain and on the source of the penicillinase. The products of the reaction have no antibiotic activity, and both the discovery and... 

The first antibiotic resistance mechanism described was that of penicillinase. Its presence and activity were first reported by Abraham and Chain in 1940 shortly after its discovery (Abraham and Chain 1940). 

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