DAVID H. SMITH, M.D.
Resistance (R) factors were discovered in 1959 in Japan during studies on the problem of multiple drug-resistant Shigella that had developed in that country. Natural isolates of Shigella resistant to sulfadiazine, streptomycin, tetracycline, and chloramphenicol had become increasingly prevalent since their description in 1955, and many related epidemiological observations could not be explained by the classical theory—that is, spontaneous mutation and selection—of the origin of drug resistance in bacteria. Japanese scientists boldly proposed and demonstrated, therefore, that these drug resistances were mediated by an extrachromosomal genetic element or episome—the R factor—transferable between gram-negative bacteria by a mating process known as
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SMITH DH. The Current Status of R Factors. Ann Intern Med. 1967;67:1337–1341. doi: 10.7326/0003-4819-67-6-1337
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Published: Ann Intern Med. 1967;67(6):1337-1341.
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