THE CLOSTRIDIUM-PERFRINGENS TET-P DETERMINANT COMPRISES 2 OVERLAPPINGGENES - TETA(P), WHICH MEDIATES ACTIVE TETRACYCLINE EFFLUX, AND TETB(P), WHICH IS RELATED TO THE RIBOSOMAL PROTECTION FAMILY OF TETRACYCLINE-RESISTANCE DETERMINANTS

The complete nucleotide sequence and mechanism of action of the tetrac ycline-resistance determinant, Tet P, from Clostridium perfringens has been determined. Analysis of the 4.4kb of sequence data revealed the presence of two open reading frames, designated as tetA(P) and tetB(P) . The tetA(P) gene appears to encode a 420 amino acid protein (molecul ar weight 46079) with twelve transmembrane domains. This gene was show n to be responsible for the active efflux of tetracycline from resista nt cells. Although there was some amino acid sequence similarity betwe en the putative TetA(P) protein and other tetracycline efflux proteins , analysis suggested that TetA(P) represented a different type of effl ux protein. The tetB(P) gene would encode a putative 652 amino acid pr otein (molecular weight 72639) with significant sequence similarity to Tet(M)-like cytoplasmic proteins that specify a ribosomal-protection tatracycline-resistance mechanism. In both C. perfringens and Escheric hia coli, tetB(P) encoded low-level resistance to tetracycline and min ocycline whereas tetA(P) only conferred tetracycline resistance. The t etA(P) and tetB(P) genes appeared to be linked in an operon, which rep resented a novel genetic arrangement for tetracycline-resistance deter minants. It is proposed that tetB(P) evolved from the conjugative tran sfer into C. perfringens of a tet(M)-like gene from another bacterium.