Drug Resistance of Staphylococci 263 



1946), and are thus of little significance in infective processes. 

 The gradual development and loss of resistance, together 

 with the extreme morphological variations seen in the early 

 stages, suggest that physiological adaptation may play some 

 part in the origin of penicillin-tolerant strains. 



Penicillin-dependent staphylococci are encountered quite 

 frequently in association with penicillin-tolerant strains when 

 penicillin-sensitive staphylococci are passaged in penicillin 

 in vitro. They show similar changes in morphology, cultural 

 characteristics and virulence, but owing to their extreme 

 instability are difficult to study. The concentration of peni- 

 cillin necessary for optimal growth is variable, but often 

 approximates to the minimal inhibitory concentration for 

 growth of the parent strain. There is no detectable loss of 

 penicillin in the surrounding medium after growth of a peni- 

 cillin-dependent strain (Barber, 1953a and h). Jackson (1953) 

 showed that growth of a penicillin-dependent strain of 

 staphylococcus was inhibited by traces of oleate in the culture 

 medium, and that if this were removed by shaking the medium 

 with a fat-solvent, the strain ceased to be penicillin-dependent. 

 He thus concluded that penicillin in some way protected the 

 strain against the toxicity of oleate. 



Penicillin-destructive strains are the almost invariable cause 

 of penicillin-resistant staphylococcal infection (Kirby, 1944; 

 Spink, Hall and Ferris, 1945; Bondi and Dietz, 1945; Gots, 

 1945; Barber and Rozwadowska-Dowzenko, 1948; Martyn, 

 1949; Forbes, 1949; Barber and Whitehead, 1949). They 

 resemble penicillin-sensitive strains of staphylococci in all 

 respects except the capacity to produce an enzyme, penicil- 

 linase, which inactivates penicillin (Barber, 1947). Resistance 

 of this type is comparatively stable, but when subcultured in 

 vitro penicillin-destroying strains tend to yield an increasing 

 proportion of variants which have completely lost the 

 capacity to produce penicillinase, and are as sensitive to 

 penicillin as the Oxford staphylococcus (Barber, 1949; Bondi, 

 Kornblum and Phalle, 1953; Fairbrother, Parker and Eaton, 

 1954). 



