Pathways & interactions
Tetracycline resistance protein TetB/drug resistance transporter (IPR001411)
Short name: Tet-R_TetB/Drug-R_transptr
The antibiotic tetracycline has a broad spectrum of activity, acting to inhibit bacterial protein synthesis by binding to the 30S ribosomal subunit, which prevents the association of the aminoacyl-tRNA to the ribosomal acceptor A site. Tetracycline binding is reversible, therefore diluting out the antibiotic can reverse its effects. Tetracycline resistance genes are often located on mobile elements, such as plasmids, transposons and/or conjugative transposons, which can sometimes be transferred between bacterial species. In certain cases, tetracycline can enhance the transfer of these elements, thereby promoting resistance amongst a bacterial colony. There are three types of tetracycline resistance: tetracycline efflux, ribosomal protection, and tetracycline modification [PMID: 16887689, PMID: 15837373]:
- Tetracycline efflux proteins belong to the major facilitator superfamily. Efflux proteins are membrane-associated proteins that recognise and export tetracycline from the cell. They are found in both Gram-positive and Gram-negative bacteria [PMID: 1423217]. There are at least 22 different tetracycline efflux proteins, grouped according to sequence similarity: Group 1 are Tet(A), Tet(B), Tet(C), Tet(D), Tet(E), Tet(G), Tet(H), Tet(J), Tet(Z) and Tet(30); Group 2 are Tet(K) and Tet(L); Group 3 are Otr(B) and Tcr(3); Group 4 is TetA(P); Group 5 is Tet(V). In addition, there are the efflux proteins Tet(31), Tet(33), Tet(V), Tet(Y), Tet(34), and Tet(35).
- Ribosomal protection proteins are cytoplasmic proteins that display homology with the elongation factors EF-Tu and EF-G. Protection proteins bind the ribosome, causing an alteration in ribosomal conformation that prevents tetracycline from binding. There are at least ten ribosomal protection proteins: Tet(M), Tet(O), Tet(S), Tet(W), Tet(32), Tet(36), Tet(Q), Tet(T), Otr(A), and TetB(P). Both Tet(M) and Tet(O) have ribosome-dependent GTPase activity, the hydrolysis of GTP providing the energy for the ribosomal conformational changes.
- Tetracycline modification proteins include the enzymes Tet(37) and Tet(X), both of which inactivate tetracycline. In addition, there are the tetracycline resistance proteins Tet(U) and Otr(C).
The expression of several of these tet genes is controlled by a family of tetracycline transcriptional regulators known as TetR. TetR family regulators are involved in the transcriptional control of multidrug efflux pumps, pathways for the biosynthesis of antibiotics, response to osmotic stress and toxic chemicals, control of catabolic pathways, differentiation processes, and pathogenicity [PMID: 15944459]. The TetR proteins identified in over 115 genera of bacteria and archaea share a common helix-turn-helix (HTH) structure in their DNA-binding domain. However, TetR proteins can work in different ways: they can bind a target operator directly to exert their effect (e.g. TetR binds Tet(A) gene to repress it in the absence of tetracycline), or they can be involved in complex regulatory cascades in which the TetR protein can either be modulated by another regulator or TetR can trigger the cellular response.
This entry includes tetracycline resistance proteins Tet(B). Tet(B) is a tetracycline efflux protein that functions as a metal-tetracycline/H+ antiporter [PMID: 11053399]. This is an energy-dependent process that decreases the accumulation of the antibiotic in whole cells. Tet(B) is an integral membrane protein with twelve potential transmembrane domains.
This entry also includes other members of the major facilitator family, including putative multidrug resistance protein MdtD (that like TetB belongs to the TCR/tet subfamily) and drug resistance transporters of the EmrB/QacA subfamily.
- PR01036 (TCRTETB)