Tetracycline antibiotics and resistance mechanisms

@article{Nguyen2014TetracyclineAA,
  title={Tetracycline antibiotics and resistance mechanisms},
  author={Fabian Nguyen and Agata L. Starosta and Stefan Arenz and Daniel Sohmen and Alexandra D{\"o}nh{\"o}fer and Daniel N. Wilson},
  journal={Biological Chemistry},
  year={2014},
  volume={395},
  pages={559 - 575}
}
Abstract The ribosome and protein synthesis are major targets within the cell for inhibition by antibiotics, such as the tetracyclines. The tetracycline family of antibiotics represent a large and diverse group of compounds, ranging from the naturally produced chlortetracycline, introduced into medical usage in the 1940s, to second and third generation semi-synthetic derivatives of tetracycline, such as doxycycline, minocycline and more recently the glycylcycline tigecycline. Here we describe… 
Antibiotics inhibiting bacterial protein synthesis, and novel resistance mechanisms
The ribosome and protein synthesis are major targets within the cell for inhibition by antibiotics, such as the tetracyclines. The tetracycline family of antibiotics represent a large and diverse
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This review summarizes the recent advances in the understanding of protein synthesis, particularly with respect to X-ray and cryoelectron microscopy structures of ribosome complexes, and highlights the different steps of translation that are targeted by the diverse array of known antibiotics.
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Protein synthesis is a major target within the bacterial cell for antibiotics. Investigations into ribosome-targeting antibiotics have provided much needed functional and structural insight into
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An overview for common mechanisms of resistance to translation-targeting drugs is provided and several important breakthroughs in recent drug development are summarized.
High Levels of Intrinsic Tetracycline Resistance in Mycobacterium abscessus Are Conferred by a Tetracycline-Modifying Monooxygenase
TLDR
The mechanism of tetracycline resistance in Mycobacterium abscessus is elucidates, the use of an inhibitor is demonstrated, and tigecycline is shown to be a poor substrate of MabTetX but also is incapable of inducing the expression of MABTet X, the first demonstration of a tetrACYcline-inactivating enzyme in mycobacteria.
The ABC of Ribosome-Related Antibiotic Resistance
TLDR
Strong evidence is provided that ABC-F proteins conferring antibiotic resistance utilize ribosome protection mechanisms, namely, by interacting with the ribosomes and displacing the drug from its binding site, thus revealing a novel role for ABC- F proteins in antibiotic resistance.
Ribosome protection by antibiotic resistance ATP-binding cassette protein
TLDR
Characterization of MsrE protein bound to the bacterial ribosome is first of its kind for ARE ABC-F members, and sheds light on the ribosomal protection mechanism by domain linker-mediated conformational change and displacement leading to drug release, suggesting a mechanism shared by other AREABC-F proteins.
Tetracycline-Inactivating Enzymes
TLDR
The current state of knowledge on the structure, mechanism, and inhibition of tetracycline-inactivating enzymes is reviewed.
A Complementary Mechanism of Bacterial mRNA Translation Inhibition by Tetracyclines
TLDR
This study describes a new complementary mechanism by which Tetracyclines may inhibit bacterial protein synthesis by allosterically perturbing the IF3 layout on the 30S, retaining IF1 during 70S IC formation, and slowing the transition toward translation elongation.
The Development of Third-Generation Tetracycline Antibiotics and New Perspectives
TLDR
The tetracycline antibiotic class has acquired new valuable members due to the optimisation of the chemical structure, and new derivatives are developed and studied primarily for the antibiotic effect and other biological effects.
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