Development And Transfer Of Antibiotic Resistance

It is clear that the development of resistance to antibiotics can be accomplished in many ways.[1'2] Mutations that alter antibiotic targets are a common mechanism, and these mutations occur at a background mutation rate in the absence of selection pressure. Organisms can also become resistant by acquiring a resistance gene or genes from other organisms by horizontal transfer. DNA carrying the gene(s) can be acquired from other microbes by: 1) conjugation, direct cell-to-cell transfer of DNA through a membrane protein complex; 2) transduction with a bacteriophage; and 3) transformation, the uptake of naked DNA from the environment. Conjugative DNA elements that carry antibiotic resistance genes include plasmids and conjugative transposons. These genetic elements can carry more than one antibiotic resistance gene, contributing to multidrug resistance. In animal agriculture, these plasmids containing multiple antibiotic resistance genes are often seen in E. coli, and the plasmids can often be very large (>50 kb). Tetracycline, florfenicol, and p-lactamase resistance genes are often found on these plasmids. Integrons are another genetic element responsible for the evolution of multidrug resistance.[7] These elements carry cassettes of genes that can integrate into plasmids or other genetic elements, thus contributing to multidrug resistance. Integrons commonly possess a sulfonamide resistance gene, sull, in the 3' conserved region, and thus sulfonamide resistance is often used as a potential indicator of the presence of integrons. Within the gene cassettes, genes conferring resistance to extended-spectrum p-lactamases, aminoglycosides, trimethoprim, and macrolides have been reported. Finally, the multidrug resistance of Salmonella enterica typhimurium DT104 deserves special mention.[8] The standard resistance phenotype in Salmonella DT104 includes resistance to ampicillin, chloramphenicol, streptomycin, sulfonamides, and tetracylines (ACSSuT). Some of the genes conferring this resistance in Salmonella DT104 are located within gene cassettes within integrons. All of the resistance genes are located together in the chromosome and form what is known as a genomic island. Typically, this chromosomal antibiotic resistance gene cluster is thought to be stable and nonmobile, and thus a clonal spread of Salmonella DT104 is required for the dissemination of this gene cluster. However, recent evidence of very similar multidrug resistance gene clusters in other Salmonella suggests the possibility that this gene cluster can be horizontally transferred.

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