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Oxazolidinones: mechanisms of resistance and mobile genetic elements involved

Andrea Brenciani1, Gianluca Morroni1, Stefan Schwarz2,3,4

  • 1Unit of Microbiology, Department of Biomedical Sciences and Public Health, Polytechnic University of Marche Medical School, Ancona, Italy.

The Journal of Antimicrobial Chemotherapy
|August 21, 2022
PubMed

Insights

Oxazolidinones are crucial last-resort antibiotics. Resistance is emerging due to gene acquisition on mobile genetic elements, threatening their effectiveness against Gram-positive bacterial infections.

Area of Science:

  • Microbiology
  • Molecular Biology
  • Antimicrobial Resistance

Background:

  • Oxazolidinones (linezolid, tedizolid) are vital last-resort antibiotics for severe Gram-positive bacterial infections.
  • These drugs inhibit bacterial protein synthesis by targeting the ribosome's peptidyl transferase center.
  • While most Gram-positive bacteria remain susceptible, oxazolidinone resistance is a growing global concern.

Purpose of the Study:

  • To review current knowledge on oxazolidinone resistance mechanisms in bacteria.
  • To provide an overview of mobile genetic elements (MGEs) associated with oxazolidinone resistance genes.
  • To highlight the role of MGEs in the spread of resistance.

Main Methods:

  • Literature review of scientific publications on oxazolidinone resistance.
  • Analysis of reported mechanisms of resistance, including mutations and acquired genes.
  • Examination of the diversity and types of mobile genetic elements involved.

Main Results:

  • Oxazolidinone resistance arises from mutations in 23S rDNA genes and ribosomal proteins.
  • Acquisition of resistance genes (cfr, cfr-like, optrA, poxtA) is a major driver of resistance.
  • These resistance genes are frequently located on various mobile genetic elements (plasmids, transposons, ICEs, prophages).

Conclusions:

  • Mobile genetic elements play a critical role in the dissemination of oxazolidinone resistance genes.
  • Understanding the diversity of MGEs is crucial for combating the spread of resistance.
  • Continued surveillance and research are needed to address the threat of oxazolidinone resistance.

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