Experiments on adaptive variation and rejuvenation:Bacillus dysenteriaeFlexner, grown on media containing sulphanilamide, acriflavine, argyrol, neosalvarsan and no drug

Abstract

Bacillus dysenteriaeFlexner(Shigella paradysentriae)grown on Lemco agar plates (without peptone) containing sulphanilamide 1/20,000 to 1/10,000 forms papillae which on subculture yield two strains: (1) the original strain unmodified and (2) a strain resistant to SA.The latter has arisen by discontinuous variation. There are no forms intermediate between strain (1) and strain (2).In one such case (Exp. 1, p. 334) the no-contact race, the unmodified non-resistant strain from the primary sulphanilamide plate and the resisting variant strain were titrated in broth containing sulphanilamide in ten increasing concentrations from 1/34,000 to 1/5000. The first two strains, the no-contact and the unmodified non-resistant from the sulphanilamide plate grew in SA 1/34,000 and failed in 1/21,000, while the resisting variant grew up to the tube containing SA 1/6000 and failed to grow in 1/5000.On plates containing sulphanilamide this adaptive variation takes place only in the papillae. It can also take place in broth containing, for example, SA 1/20,000 to 1/10,000.There is no such thing as gradual progressive acquisition of resistance by the whole of a bacterial population exposed to a drug. Such phrases as ‘teaching bacteria to resist’ are misleading and anthropomorphic and should not be employed.Fluid cultures which show a progressive gradual increase of resistance do so as a result of an increasing percentage of resistant cells in a mixed population of resistant and non-resistant bacteria. Experiments in fluid media should always be checked and the growth analysed by plating.Resistant strains maintain this character after prolonged growth on drug-free media.(2) Flexner's dysentery bacillus grown on plates containing acriflavine 1/60,000 to 1/40,000 forms in papillae strains resistant to this drug. The non-papillary areas of colonies die early, viz. on the 3rd day. The variation in this case also is discontinuous.(3) On the other hand, if Flexner's bacillus is grown on agar containing organic compounds of silver or arsenic (argyrol or neosalvarsan), it forms no variants resisting these drugs.(4) Papillae possess two biological functions:(a)they are the site of adaptive variation in response to elements in their environment, such as harmful drugs or useful sugars; (6) they are also the site of rejuvenation of senile cells and of cells affected by common unfavourable conditions such as exhaustion of food supply and accummulation, of excretory substances.The greatest development of papillae takes place on plates which form no variants, such as plates of drug-free agar, agar plates containing sulphanilamide sown with strains resistant to sulphanilamide and plates containing organic compounds of silver or arsenic.