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Tetracycline destructases, most notably Tet(X) and its variants, are **flavin-dependent monooxygenase enzymes** found primarily in Gram-negative bacteria but also reported in Gram-positive species. They confer resistance by directly modifying and inactivating a broad range of tetracycline antibiotics, including the newest-generation drugs such as tigecycline. Over a dozen Tet(X) variants have now been described, with varying substrate profiles and resistance levels; some catalyze inactivation of all clinically used tetracyclines. These enzymes pose a major public health concern due to their ability to propagate via mobile genetic elements, making bacteria less susceptible or refractory to tetracycline-based therapies[4][5][9].
Enzymatic oxidation/inactivation: Tet(X) variants catalyze NADPH- and FAD-dependent hydroxylation or oxidation of tetracyclines, leading to antibiotic degradation and loss of activity[4][5].
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