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Tetracycline-Inactivating Enzymes

Jana L Markley1, Timothy A Wencewicz1

  • 1Department of Chemistry, Washington University in St. Louis, St. Louis, MO, United States.

Frontiers in Microbiology
|June 15, 2018
PubMed

Insights

New tetracycline antibiotics face threats from emerging enzymatic inactivation resistance. This review covers the structure, mechanism, and inhibition of these enzymes, crucial for next-generation antibiotic development.

Area of Science:

  • Antibiotic resistance
  • Medicinal chemistry
  • Enzymology

Background:

  • Tetracyclines are established antibacterial agents with a long history.
  • Advancements in synthesis and scaffold modification aim to overcome existing resistance.
  • Emerging resistance mechanisms, like enzymatic inactivation, pose a significant threat to new tetracyclines.

Purpose of the Study:

  • To review the current understanding of tetracycline-inactivating enzymes.
  • To discuss the structure and mechanism of these enzymes.
  • To explore strategies for inhibiting tetracycline-inactivating enzymes.

Main Methods:

  • Literature review of scientific publications.
  • Analysis of enzyme structures and mechanisms.
  • Synthesis of information on inhibition strategies.

Main Results:

  • Tetracycline-inactivating enzymes represent a growing challenge to next-generation tetracyclines.
  • Understanding enzyme structure and mechanism is key to developing inhibitors.
  • Several strategies for enzyme inhibition are being explored.

Conclusions:

  • Inhibition of tetracycline-inactivating enzymes is critical for the clinical success of new tetracycline antibiotics.
  • Further research into enzyme mechanisms and inhibitor development is necessary.
  • Combating enzymatic inactivation is essential for preserving the utility of tetracyclines.
Keywords:
antibiotic adjuvantsantibiotic resistanceenzymatic antibiotic inactivationflavin monooxygenasetetracycline destructasestetracyclines

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