Evolution of plasmids in vivo in a strain of Staphylococcus aureus.

A strain of Staphylococcus aureus (no. FAR4) has been isolated from a 
patient at frequent intervals over 18 months. This strain has previously 
been shown to lose resistance to several antibodies (Lacey et al., 
1973); during the last 6 months further changes have occurred in 
it in vivo. Lincomycin resistance appeared after the patient had been 
treated with clindamycin. This was due to mutation to constitutive resistance 
to both lincomycin and erythromycin at a locus adjacent to that 
determining "inducible" resistance to erythromycin. Both loci are probably carried by 
an extrachromosomal element. Three types of variation in the PF plasmid 
were observed. Alteration in production of penicillinase from macroconstitutive to microconstitutive, 
was not associated with any detectable change in plasmid size. This 
change gave the cell an advantage in vitro, because it was 
associated with a faster growth rate and probably also in vivo, 
because the microconstitutive variants were isolated in increasing numbers after flucloxacillin 
therapy had ceased. Complete loss of determinants for penicillinase production and 
for resistance to cadmium ions from the PF plasmid was associated 
with a decrease in plasmid size of about 4 x 10 
6 daltons. This change was also associated with increased growth rate 
in vitro. Loss of resistance to fusidic acid from the PF 
plasmid was associated with a decrease in plasmid size of about 
1 x 10 6 daltons. 