Ribosomal protection proteins and their mechanism of tetracycline resistance.

Ribosomal protection represents an important tactic for promoting tetracycline resistance in both gram-positive and -negative species. Tet(O) and Tet(M) are the best studied of these determinants and were originally isolated from Campylobacter jejuni and Streptococcus spp., respectively, although both are widely distributed (10). These are the only two ribosomal protection proteins (RPPs) that have been studied in detail, and therefore, they have been dealt with extensively in this review. It is assumed, however, that the other members of this class of RPPs [Tet(S), Tet(T), Tet(Q), TetB(P), Tet(W), and OtrA] function through similar mechanisms. The distribution of these determinants in the eubacteria has been extensively reviewed by Chopra and Roberts (10) and more recent information can also be found at http://faculty.washington.edu/ marilynr/. Although this review focuses primarily on RPPs, it should be noted that a great variety of tetracycline resistance mechanisms exist (for a review, see reference 10). These determinants include (i) the efflux-based mechanisms found in grampositive and gram-negative bacteria (10), (ii) the enzymatic degradation of tetracyclines found in Bacteroides (46), (iii) the rRNA mutations found in Propionibacterium acnes and Helicobacter pylori (19, 40, 55), and (iv) a host of undetermined mechanisms which bear little resemblance to the well-documented determinants mentioned above (10). In this review, we will survey recent advances in the study of the ribosome, tetracycline, and the RPPs that further the understanding of RPP activity. Earlier work dealing with Tet(M) and Tet(O) as well as the other RPPs has been reviewed previously (51, 52).