Emerging High-Level Tigecycline Resistance: Novel Tetracycline Destructases Spread via the Mobile Tet(X)

Bioessays. 2020 Aug;42(8):e2000014. doi: 10.1002/bies.202000014. Epub 2020 Jun 22.

Abstract

Antibiotic resistance in bacteria has become a great threat to global public health. Tigecycline is a next-generation tetracycline that is the final line of defense against severe infections by pan-drug-resistant bacterial pathogens. Unfortunately, this last-resort antibiotic has been challenged by the recent emergence of the mobile Tet(X) orthologs that can confer high-level tigecycline resistance. As it is reviewed here, these novel tetracycline destructases represent a growing threat to the next-generation tetracyclines, and a basic framework for understanding the molecular epidemiology and resistance mechanisms of them is presented. However, further large-scale epidemiological and functional studies are urgently needed to better understand the prevalence and dissemination of these newly discovered Tet(X) orthologs among Gram-negative bacteria in both human and veterinary medicine.

Keywords: Tet(X); high-level tigecycline resistance; pan-drug-resistant; plasmid reservoirs; plasmid-encoding tigecycline enzymatic inactivation; tetracycline antibiotics; tetracycline destructases.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Anti-Bacterial Agents* / pharmacology
  • Humans
  • Microbial Sensitivity Tests
  • Plasmids
  • Tetracycline*
  • Tetracyclines / pharmacology
  • Tigecycline

Substances

  • Anti-Bacterial Agents
  • Tetracyclines
  • Tigecycline
  • Tetracycline