Tetracyclines efflux

Plasmid- or transposon-encoded tetracycline efflux proteins have been described in a number of bacteria. These efflux profeins are fhoughf to span fhe cytoplasmic membrane and are dependenf on the proton-motive force for their action, ft is thought that the efflux proteins bind tetracyclines and initiate proton transfer, although no functional domains have been identified. Eight distinct tetracycline efflux profeins have been idenfified thus far. 

In some cases, catechins can also act in synergistic mode when used in association with currently used antibiotic molecules (Table 2). EGCG exhibited synergy with /3-lactams. Sudano Roccaro et al. [73] found that this compound is able to reverse tetracycline resistance in Staphylococcus epidermidis and S. aureus isolates. This synergistic interaction has been explained by inhibition of tetracycline efflux pump activity in microbial cells resulting in an... 

Cheng, J., Hicks, D. B. and Krulwich, T. A. (1996). The purified Bacillus subtilis tetracycline efflux protein TetA(L) reconstitutes both tetracycline-cobalt/H+ and Na+(K+)/H+ exchange, Proc. Natl Acad. Sci. USA, 93, 14446-14451. 

Gene encoding a repressor protein, which regulates the tetracycline efflux system genes Trimethoprim... 

S. B., Inhibition of the tetracycline efflux antiport protein by 13-thio-substituted 5-hy-droxy-6-deoxytetracycline, J. Med. Chem... 36,. 370, 199.3. 

More recently possible roles in supporting pH homeostasis and alkali tolerance have been suggested for TetL, which is a tetracycline efflux protein from Bacillus subtilis, and the multidrug transporter MdfA (71). 

Aldema ML, McMurry LM, Walmsiey AR, Levy SB. Purification of the TnlO-specified tetracycline efflux antiporter, TetA, in a native state as a polyhistidine fusion protein. Mol Microbiol 1996 19 187-195. 

Sloan J, McMurry LM, Lyras D. Levy SB, Rood 1. The Closmdium perfringeta TetP determi-nan( comprises 2 overlaf ing genes—tetA(P), which mediates active tetracycline efflux, and letB(P), which is related to the libosomal protection family of tettacycline resistance deter minants. Mol Microbiol 1996 11 403-415. 

Guay GG, Tucktnan M, Rothstein DM. Mutations in the TetA(B) gene that cause a change in substrate-specificity of the tetracycline efflux pump. Antimicrob Agents Chemother 1994 38 857-860. 

Sheridan RP, Chopra 1, Origin of tetracycline efflux proteins—conclusions from nucleotide-sequence analysis. Mol Microbiol 1991 5 895-900. 

Fig. 4. Comparison of the three types of tetracycline resistance where T represents the tetracycline molecule O, a tetracycline transporter and aaa/, the ribosome A shows the effect of tetracycline exposure on a sensitive cell B, the efflux of resistance where a cytoplasmic membrane protein ( D) pumps tetracycline out of the cell as fast as the tetracycline transporter takes it up C, the ribosomal protection type of resistance where the ribosome is modified by ( ) to block productive binding and D, the tetracycline modification type of resistance where t is an inactive form of tetracycline. Reproduced with...

A more recently recognized mechanism of dmg resistance is that of efflux in which the antibiotic is rapidly extmded horn the cell by an energy-dependent mechanism. This affects antibiotics such as the tetracyclines and macrolides. 

Antibiotic efflux Tetracyclines Energy-dependent efflux of accumulated drugs... 

Genes encoding efflux pumps confer resistance to tetracyclines Genes encoding proteins protecting the ribosome from the inhibiting effects of tetracycline... 

Tetracyclines Minocycline Tigecycline Monooxygenation Efflux Altered target... 

Resistance is related largely to changes in cell permeability and a resultant decreased accumulation of drug due to increased efflux from the cell by an energy-dependent mechanism. Other mechanisms, such as production of a protein that alters the interaction of tetracycline with the ribosome and enzymatic inactivation of the drug, have been reported. 

Mechanisms of Resistance. Three distinct biochemical mechanisms of resistance to tetracyclines have been identified. The energy-dependent efflux of antibiotic mediated by resistance proteins located in the bacterial... 

Three mechanisms of resistance to tetracycline have been described (1) decreased intracellular accumulation due to either impaired influx or increased efflux by an active transport protein pump (2) ribosome protection due to production of proteins that interfere with tetracycline binding to the ribosome and (3) enzymatic inactivation of tetracyclines. The most important of these is production... 

Tetracycline was effective against gynecologic infection due to bacteroides, but now these organisms are resistant due to the presence of plasmid-mediated protein that promotes efflux of the drug. 

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