Target protection as a key antibiotic resistance mechanism

Nat Rev Microbiol. 2020 Nov;18(11):637-648. doi: 10.1038/s41579-020-0386-z. Epub 2020 Jun 25.


Antibiotic resistance is mediated through several distinct mechanisms, most of which are relatively well understood and the clinical importance of which has long been recognized. Until very recently, neither of these statements was readily applicable to the class of resistance mechanism known as target protection, a phenomenon whereby a resistance protein physically associates with an antibiotic target to rescue it from antibiotic-mediated inhibition. In this Review, we summarize recent progress in understanding the nature and importance of target protection. In particular, we describe the molecular basis of the known target protection systems, emphasizing that target protection does not involve a single, uniform mechanism but is instead brought about in several mechanistically distinct ways.

Publication types

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

MeSH terms

  • Anti-Bacterial Agents* / chemistry
  • Anti-Bacterial Agents* / metabolism
  • Bacteria / chemistry
  • Bacteria / drug effects
  • Bacteria / metabolism
  • Bacterial Proteins* / chemistry
  • Bacterial Proteins* / metabolism
  • Carrier Proteins / chemistry
  • Carrier Proteins / metabolism
  • Drug Resistance, Bacterial / physiology*
  • Models, Molecular*


  • Anti-Bacterial Agents
  • Bacterial Proteins
  • Carrier Proteins
  • Tet O resistance protein, Bacteria