Antibacterial mechanisms and efficacy of sarecycline in animal models of infection and inflammation

Christopher G. Bunick, Jonette Keri, S. Ken Tanaka, Nika Furey, Giovanni Damiani, Jodi L. Johnson, Ayman Grada*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Prolonged broad-spectrum antibiotic use is more likely to induce bacterial resistance and dysbiosis of skin and gut microflora. First and second-generation tetracycline-class antibiotics have similar broad-spectrum antibacterial activity. Targeted tetracycline-class antibiotics are needed to limit antimicrobial resistance and improve patient outcomes. Sarecycline is a narrow-spectrum, thirdgeneration tetracycline-class antibiotic Food and Drug Administration (FDA)-approved for treating moderate-to-severe acne. In vitro studies demonstrated activity against clinically relevant Grampositive bacteria but reduced activity against Gram-negative bacteria. Recent studies have provided insight into how the structure of sarecycline, with a unique C7 moiety, interacts with bacterial ribosomes to block translation and prevent antibiotic resistance. Sarecycline reduces Staphylococcus aureus DNA and protein synthesis with limited effects on RNA, lipid, and bacterial wall synthesis. In agreement with in vitro data, sarecycline demonstrated narrower-spectrum in vivo activity in murine models of infection, exhibiting activity against S. aureus, but reduced efficacy against Escherichia coli compared to doxycycline and minocycline. In a murine neutropenic thigh wound infection model, sarecycline was as effective as doxycycline against S. aureus. The anti-inflammatory activity of sarecycline was comparable to doxycycline and minocycline in a rat paw edema model. Here, we review the antibacterial mechanisms of sarecycline and report results of in vivo studies of infection and inflammation.

Original languageEnglish (US)
Article number439
JournalAntibiotics
Volume10
Issue number4
DOIs
StatePublished - 2021

Keywords

  • Acne
  • Animal models
  • Antibiotic
  • Antibiotic resistance
  • Infection
  • Inflammation
  • Narrow-spectrum
  • Sarecycline
  • Tetracyclines

ASJC Scopus subject areas

  • Microbiology
  • Biochemistry
  • Pharmacology, Toxicology and Pharmaceutics(all)
  • Microbiology (medical)
  • Infectious Diseases
  • Pharmacology (medical)

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