Evolution of the phenomenon of drug-resistance III. The origin of the development of resistance to sulphathiazole in Escherichia coli and Staphylococcus aureus

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Abstract
This study deals with the hourly determination of metabolic differences during growth with sulphathiazole (ST) between the ST-sensitive and ST-resistant strains of Escherichia coli and Staphylococcus aureus for the timing of the onset of resistance mechanism. The amounts of the extracellularly accumulated p-aminobenzoic acid (PAB), folic acid (FA) and citrovorum factor (CF) in the culture fluids and the growth rates are determined. As described in the preceding paper, the sequence of metabolic events with these strains is of the same pattern. The PAB curve in the resistant cell system with ST rises perpendicularly to a peak and then declines sharply followed by the rise of the growth curve. In contrast, in the sensitive cell system with ST, the PAB curve, after reaching a peak, forms a longlasting plateau or a dome-like plateau. During these plateau periods growth is absent. The decline in the plateau is followed by growth. In both the sensitive and resistant strains (E. coli), the extracellularly accumulated PAB are quantitatively alike. Nevertheless, the PAB in the sensitive system is incapable of antagonizing ST which is of from 10- to 20-fold smaller amount than in the resistant system. As the antagonism of PAB to ST takes place the PAB curve declines and growth is initiated. These events are coincidental with the acquisition of resistance to ST during the PAB plateau period. The similar events in the ST-sensitive staphylococcal strain are associated with the development of the satellism .phenomenon. This phenomenon is manifested on the agar plates with ST until resistance is acquired. The resistant staphylococcal strain does not manifest the phenomenon of satellism. The data presented here and elsewhere are extrapolated to formulate the thesis that a drug or toxic agent exercises two roles on a living system: One, the role of a negative catalyst, and two, the role of a positive catalyst. The latter neutralizes the former giving rise to the phenomenon of resistance, or the evolution of biochemical mechanisms by which a living cell survives the action of toxic agents. A toxin of bacterial or other origins functions in a manner similar to the actions of drugs on bacteria giving rise to the immunological defence mechanism.