Structural and mechanistic basis of the high catalytic activity of monooxygenase Tet(X4) on tigecycline.

ABSTRACT:

Background

Tigecycline is a tetracycline derivative that constitutes one of the last-resort antibiotics used clinically to treat infections caused by both multiple drug-resistant (MDR) Gram-negative and Gram-positive bacteria. Resistance to this drug is often caused by chromosome-encoding mechanisms including over-expression of efflux pumps and ribosome protection. However, a number of variants of the flavin adenine dinucleotide (FAD)-dependent monooxygenase TetX, such as Tet(X4), emerged in recent years as conferring resistance to tigecycline in strains of Enterobacteriaceae, Acinetobacter sp., Pseudomonas sp., and Empedobacter sp. To date, mechanistic details underlying the improvement of catalytic activities of new TetX enzymes are not available.

Results

In this study, we

SUBMITTER: Cheng Q 

PROVIDER: S-EPMC8666040 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature