Epidemiological and genetical study of drug resistance in Staphylococcus aureus.

Surveys of staphylococcal strains, isolated from clinical sources in geographically scattered hospitals in Japan, disclosed the following facts: 1) Triple (TC·SM·SA, TC·PC· SA, PC·SM·SA) and quadruple (TC·SM·PC·SA) resistant strains with reference to TC, SM, PC and SA, were manifest and they were restricted to specific phage group. 2) There is a maximum population of resistant strains (M.P.R.) in a restricted area, which is governed by the amount and period of use of a drug and by genetic characters of the bacteria such as the mutation rate to resistance, and character which governs infectivity and ability for successful parasitism. 3) There are two types of resistant strains: the first becomes resistant easily and consequently multiple resistant when a new drug is introduced, and consists largely of strains in phage group I containing phage type 80/81. The second type remains single (SA) or double (PC·SA; SM·SA) resistant, and consists primarily of strains in group II and III From the facts that all of the tested staphylococcal strains from clinical sources carry prophages and their drug resistance can be transduced to other strains by their prophages, the present author presents the hypothesis that transduction of drug resistance by prophage is mainly responsible for the acquisition of multiple resistance and wide distribution of multiple resistant strains in phage type or phage group. Genetic studies of drug resistance in staphylococci have disclosed the following facts: 1) Resistance to TC is easily transduced at high frequencies by prophages obtained from multiple resistant strains, and in various combinations of donors and recipients. Resistance to SA and SM is jointly transduced with TC, and vice donors and recipients. Resistance to SA and SM is jointly transduced with TC, and vice versa. Resistance to PC, the ability to form penicillinase (PCase), and chloramphenicol (CM) resistance is not transduced jointly with resistance to TC, SM, and SA. 2) Resistance to macrolide (Mac) antibiotics (EM, OM, LM, SP) is eliminated jointly and irreversibly by acriflavine treatment or by ultraviolet irradiation, and is transduced jointly by phages obtained from donor strains. From these results it can be concluded that Mac resistance is located on an extrachromosomal plasmid. 3) Because of the genetic character of PCase formation (PCase+) and irreversible elimination of PCase+, it was concluded that the gene which governs PCase formation is located on a plasmid. And there are two types of plasmid; one which carries the genetic characters of resistance to macrolide antibiotics (Macr) and of the penicillinase formation (PCase+) and the other carries only PCase+. A genetic model for the genes which govern resistance to TC, SM, SA and for the plasmids is presented. 4) The genetic character which governs resistance to CM is irreversibly eliminated during storage of stock culture or by treatment with acriflavine. This fact and results from transductional analysis suggest that the gene responsible for CM resistance may be located on a plasmid, probably different from the plasmids which govern (Macr. PCase+) or (PCase+). The findings that CM resistant strains of S. aureus inactivated CM in the presence of acetylcoenzyme A strongly suggest that CM resistance in strains from clinical sources is accounted for by inactivation of CM through acetylation of the drug molecule.