SUMMARY: Tetracyclines were discovered in the 1940s and exhibited activity against a wide range of microorganisms including gram-positive and gram-negative bacteria, chlamydiae, mycoplasmas, rickettsiae, and protozoan parasites. They are inexpensive antibiotics, which have been used extensively in the prophlylaxis and therapy of human and animal infections and also at subtherapeutic levels in animal feed as growth promoters. The first tetracycline-resistant bacterium, Shigella dysenteriae, was isolated in 1953. Tetracycline resistance now occurs in an increasing number of pathogenic, opportunistic, and commensal bacteria. The presence of tetracycline-resistant pathogens limits the use of these agents in treatment of disease. Tetracycline resistance is often due to the acquisition of new genes, which code for energy-dependent efflux of tetracyclines or for a protein that protects bacterial ribosomes from the action of tetracyclines. Many of these genes are associated with mobile plasmids or transposons and can be distinguished from each other using molecular methods including DNA-DNA hybridization with oligonucleotide probes and DNA sequencing. A limited number of bacteria acquire resistance by mutations, which alter the permeability of the outer membrane porins and/or lipopolysaccharides in the outer membrane, change the regulation of innate efflux systems, or alter the 16S rRNA. New tetracycline derivatives are being examined, although their role in treatment is not clear. Changing the use of tetracyclines in human and animal health as well as in food production is needed if we are to continue to use this class of broad-spectrum antimicrobials through the present century.

This mini-review summarizes the changes in the field of bacterial acquired tetracycline resistance (tet) and oxytetracycline (otr) genes identified since the last major review in 2001. Thirty-eight acquired tetracycline resistant (Tc(r)) genes are known of which nine are new and include five genes coding for energy-dependent efflux proteins, two genes coding for ribosomal protection proteins, and two genes coding for tetracycline inactivating enzymes. The number of inactivating enzymes has increased from one to three, suggesting that work needs to be done to determine the role these enzymes play in bacterial resistance to tetracycline. In the same time period, 66 new genera have been identified which carry one or more of the previously described 29 Tc(r) genes. Included in the new genera is, for the first time, an obligate intracellular pathogen suggesting that this sheltered group of bacteria is capable of DNA exchange with non-obligate intracellular bacteria. The number of genera carrying ribosomal protection genes increased dramatically with the tet(M) gene now identified in 42 genera as compared with 24 and the tet(W) gene found in 17 new genera as compared to two genera in the last major review. New conjugative transposons, carrying different ribosomal protection tet genes, have been identified and an increase in the number of antibiotic resistance genes linked to tet genes has been found. Whether these new elements may help to spread the tet genes they carry to a wider bacterial host range is discussed.

This Minireview summarizes the changes in the field of bacterial resistance to macrolide, lincosamide, streptogramin, ketolide, and oxazolidinone (ML

Tetracyclines have been used for treatment of a wide variety of gram-positive and gram-negative bacterial infections since the 1950s. In addition to

Twenty-five distinct tetracycline-resistant gram-negative bacteria recovered from four Chilean fish farms with no history of recent antibiotic use were examined for the presence of tetracycline resistance ( tet ) genes. Sixty percent of the isolates carried 1 of the 22 known tet genes examined. The distribution was as follows. The tet (A) gene was found in six isolates. The tet (B) gene was found in two isolates, including the first description in the genus Brevundimonas . Two isolates carried the tet (34) and tet (B) genes, including the first description of the tet (34) gene in Pseudomonas and Serratia and the first description of the tet (B) gene in Pseudomonas . The tet (H) gene was found in two isolates, which includes the first description in the genera Moraxella and Acinetobacter . One isolate carried tet (E), and one isolate carried tet (35), the first description of the gene in the genus Stenotrophomonas . Finally, one isolate carried tet (L), found for the first time in the genus Morganella . By DNA sequence analysis, the two tet (H) genes were indistinguishable from the previously sequenced tet (H) gene from Tn 5706 found in Pasteurella multocida . The Acinetobacter radioresistens isolate also harbored the Tn 5706 -associated 1,063-bp IS element IS 1597 , while the Moraxella isolate carried a 1,026-bp IS-like element whose 293-amino-acid transposase protein exhibited 69% identity and 84% similarity to the transposase protein of IS 1597 , suggesting the presence of a novel IS element. The distribution of tet genes from the Chilean freshwater ponds was different than those that have previously been described from other geographical locations, with 40% of the isolates carrying unidentified tetracycline resistance genes.