Formation of Multiple Drug Resistance Factors by Recombination between Transfer Factor and Resistance Determinants

Abstract

Drug-resistance (γ) determimants, γ₂₇(tet), γ₁(cml), and γ₁₁(str. sul) were obtained from R factors, and were capable of conferring resistance to tetracycline, chloramphenicol, and to both streptomycin and sulfanilamide, respectively. They were integrated into the chromosome of Escherichin coli K12 and nontransmissible by conjugation. As described previously, the recombinant T-tet factor was tormed and conjugally transmissible when E. coli K12 γ₂₁(tet)⁺ was infected with T₉₅ one of the transfer factors. Similarly, the recombinants T-tet. cml and T-tet.str. sul factors were formed by the interaction between T-tet factor and resistance determinants γ₁(cml) and γ₁₁(str. sul), respectively Subsequently, T-tet. cml. sul factor was formed bye the recombination between T-tet. cml factor and γ₁₁(str. sul) determinant, and T-tet. str. sul. cml factor was produced by the infection of E. coli K12 γ₁(cml)⁺ with T-tet. str sul factor. These recombinants were conjugally transmissible and transduced by phage PI as one unit. These results strongly suggested the origin of R factors which were capable of conferring multiple resistance and transmissible by conjugation. According to the segrcgational patterns of resistance determinants by transduction and by conjugal transmission, the genetic structure of T-tet. cml. str. sul. factors was established as being circular and the linkage order of the determinants of these factors was described.