Tetracycline resistance determinants: mechanisms of action, regulation of expression, genetic mobility, and distribution

Abstract

Tetracycline-resistant bacteria were first isolated in 1953 from Shigella dysenteriae, a bacterium which causes bacterial dysentery. Since then tetracycline-resistant bacteria have been found in increasing numbers of species and genera. This has resulted in reduced effectiveness of tetracycline therapy over time. Tetracycline resistance is normally due to the acquisition of new genes often associated with either a mobile plasmid or a transposon. These tetracycline resistance determin~mts are distinguishable both genetically and biochemically. Resistance is primarily due to either energy-dependent efflux Of tetracycline or protection of the ribosomes from the action of tetracycline. Gram-negative tetracycline efflux proteins are linked to repressor proteins which in the absence of tetracycline block transcription of the repressor and structural effiux genes. In contrast, expression of the Gram-positive tetracycline efflux genes and some of the ribosomal protection genes appears to be regulated by attenuation of mRNA transcription. Specific tetracycline resistance genes have been identified in 32 Gram-negative and 22 Gram-positive genera, Tetracycline-resistant bacteria are found in pathogens, opportunistic and normal flora species. Tetracycline-resistant bacteria can be isolated from man, animals, food, and the environment. The nonpathogens in each of these ecosystems may play an important role as reservoirs for the antibiotic resistance genes. It is clear that if we are to reverse the trend toward increasingly antibiotic-resistant pathogenic bacteria we will need to change how antibiotics are used in both human and animal health and food production.

Wild black-headed gulls (Larus ridibundus) as an environmental reservoir of Salmonella strains resistant to antimicrobial drugs

“…The excessive use of antimicrobial drugs in human and veterinary medicine, including the administration of antibiotics as growth promoters for food animals, contributes to the emergence and dissemination of antibiotic resistance among various species of bacteria including salmonellae (Roberts 1996). In black-headed gulls, we found Salmonella strains resistant to streptomycin, sulfonamides, ampicillin, tetracycline, chloramphenicol, and nalidixic acid.…”

Molecular diversity and transferability of the tetracycline resistance gene tet(M), carried on Tn916-1545 family transposons, in enterococci from a total food chain

“…The genes encoding for tetracycline resistance are numerous but the most widely distributed tetracycline resistance determinant in Gram-positive bacteria is the tet(M) gene (Roberts 1996). Previous studies have shown the diversity of the tet(M) gene in different bacterial strains and species (Huys et al 2004;Bertrand et al 2005;Spigaglia et al 2006).…”

“…Different mechanisms are implicated in resistance against tetracycline, such as ribosome protection, encoded for example by tet(M), tet(O) and tet(S) genes, and efflux systems, encoded by tet(K) and tet(L). The widespread distribution of tet(M) in many bacterial genera, including Enterococcus (Clewell et al 1995;Roberts 1996), is often linked to the presence of conjugative transposons of the Tn916-1545 family. Mating experiments have demonstrated the ability of some Enterococcus faecalis, Enterococcus faecium and Enterococcus durans strains to transfer tetracycline resistance determinants by means of Tn916-1545 transposons (Huys et al 2004;Wilcks et al 2005;Hummel et al 2007).…”

The role of conjugative transposons in spreading antibiotic resistance between bacteria that inhabit the gastrointestinal tract

“…Some of these transfer events may have occurred long ago on an evolutionary time scale, and the genes have subsequently diverged. Many different tet(M) genes from clinical bacterial isolates, located on various plasmids and CTns, have been sequenced and shown to diverge by between 1 [39] and 8% [47] (table 3). The nonrandom distribution of nucleotide changes illustrates the existence of mosaic genes, derived from two distinct alleles, which appear to have arisen by recombination after the gene integrated into Tn916 [47].…”