TetAmediated

TetA-mediated tetracycline resistance refers to a common mechanism by which bacteria withstand tetracycline antibiotics. It is driven by the TetA family of membrane efflux proteins that function as secondary active transporters, expelling tetracycline from the cytoplasm and thereby lowering the intracellular drug concentration. This allows bacterial ribosomes to continue translating proteins in the presence of the antibiotic.

Genetic and regulatory features: The tetA gene typically encodes the TetA transporter, and its expression is often controlled by the TetR repressor. In many bacteria, tetA is located in an operon with tetR and is inducible: when tetracycline is present, the drug binds TetR, relieving repression and increasing tetA transcription. Regulatory mutations can yield constitutive expression. tetA is frequently carried on plasmids and transposable elements, such as members of the Tn10 family, facilitating horizontal gene transfer between species.

Mechanism and substrates: TetA belongs to the major facilitator superfamily and uses the proton motive force to exchange protons for tetracycline molecules across the inner membrane. This efflux reduces the intracellular concentration of the drug, protecting the ribosome. TetA can export a range of tetracycline derivatives, with varying efficiency depending on the variant; some pumps may confer reduced susceptibility to related antibiotics such as doxycycline or minocycline.

Distribution and clinical relevance: TetA-mediated resistance is widespread among Gram-negative pathogens, including Escherichia coli and Salmonella, and is a major contributor to tetracycline resistance in clinical isolates. The presence of tetA often correlates with elevated minimum inhibitory concentrations and may be linked to other resistance determinants on mobile genetic elements.

Detection and surveillance: Molecular assays targeting tetA, along with phenotypic susceptibility testing, are used to detect and monitor this resistance mechanism. The mobility of tetA via plasmids underscores the importance of stewardship to limit horizontal gene transfer of resistance traits.