The Assimilation of Amino-acids by Bacteria: 7. The Nature of Resistance to Penicillin in Staphylococcus aureus

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Abstract
SUMMARY: Penicillin blocks the assimilation of glutamic acid by Staphylococcus aureus; the effective concentration of penicillin is of the same order as that required to inhibit growth of the organism whether the culture is sensitive or resistant to penicillin. Serial subcultivation in increasing concentrations of penicillin results in the selection of resistant mutants; as resistance increases, the ability of the cells to assimilate glutamic acid decreases. The efficiency of the assimilation process in highly resistant cells is poor, but they can synthesize all their amino-acid requirements from ammonia and glucose. The decrease in assimilatory efficiency as resistance to penicillin increases is correlated with an increase in the ability of the cells to synthesize amino-acids. Reverse mutations, having decreased ability to synthesize certain amino-acids, were obtained from highly resistant strains and had increased sensitivity to penicillin. Strains of Staph, aureus requiring several amino-acids as nutrients have been ‘trained’, by subcultivation in media progressively more deficient in amino-acids, to dispense with the addition to the medium of all amino-acids other than cystine and histidine; the increase in synthetic ability was accompanied by a marked increase in penicillin resistance. It is suggested that penicillin interferes with the mechanism whereby certain amino-acids are taken into the cell, and that the sensitivity of the cell to penicillin is then determined by the degree to which its growth processes are dependent upon assimilation of preformed amino-acids rather than upon their synthesis.