Tetracycline Resistance Determinants in Gram-Positive Bacteria

Abstract

The emergence of tetracycline resistance in the mid-1950s, initially in gram-negative bacteria and then in gram-positive bacteria, resulted in the declining usefulness of tetracyclines. There are three different tetracycline resistance mechanisms of clinical importance found among gram-positive organisms. They are active efflux, ribosomal protection, and mutated rRNA. Multidrug transporters are able to efflux substrates that are chemically diverse, and some from gram-negative bacteria include tetracycline in their repertoire, for example, AcrAB (Escherichia coli) and MexAB/OprM (Pseudomonas sp.). The only multidrug transporter from gram-positive bacteria known to transport tetracycline is the TetAB transporter from Corynebacterium. The emphasis in this chapter is on proteins found in gram-positive organisms. The Asp-66–Ala mutation may directly or indirectly prevent tetracycline binding, or it may prevent a conformational change in motif A caused by binding elsewhere. In the case of the gram-positive Tet(L) and Tet(K) proteins, substitutions at Asp-74, corresponding to the essential Asp-66 in TetA(B), only partly decrease tetracycline resistance, although efflux activity is more severely affected. Tetracycline resistance determinants are widely spread among different gram-positive genera. Tetracycline resistance spreads because the determinants are often located on conjugative elements, either plasmids or transposons.