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Examination of the action of a series of surface-active polyoxyethylene ethers on the growth of the avirulent strain of Mycobacterium tuberculosis, H37 Ra, showed that one member, the ether of 2,2′-dihydroxy-5, 5′-di-tert-octyldiphenyl-methane (D4), inhibited this strain but not the virulent variant H37 Rv. This type of differential inhibition has been observed with a commercial surface-active mixture, ‘Triton A20’ (Dubos & Middlebrook, 1948). Lengthening of the polyoxyethylene chains of D4 led to loss of its inhibitory property. Both D4 and ‘Triton A20’ could induce resistance in H37 Ra, and cross-resistance to D4 of a strain resistant to ‘Triton A20’ was observed; this cross-resistance suggested that a compound closely related to D4 was the active constituent of ‘Triton A20’. The resistant strains grew in a microscopically amorphous pattern, like their parent strain.
The growth of four other avirulent strains of tubercle bacilli was inhibited, like that of H37 Ra, by D4, while two slightly virulent strains grew freely in this detergent, like H37 Rv. One factor common to the strains naturally insusceptible to D4, but absent from those inhibited, is the ability to produce some degree of microscopic ‘cord’ pattern, and this property may have some connexion with the cause of the differential inhibition by D4. Surface activity also probably plays a part.