Nanoscaled discovery of a shunt rifamycin from Salinispora arenicola using a three-colour GFP-tagged Staphylococcus aureus macrophage infection assay

Nhan Pham, Joana Alves, Fiona Sargison, Reiko Cullum, Jan Wildenhain, William Fenical, Mark S Butler, David A Mead, Brendan Duggan, Ross Fitzgerald, James J.H. St Clair, Manfred Auer

Research output: Contribution to journalArticlepeer-review

Abstract

Antimicrobial resistance has emerged as a global public health threat, and development of novel therapeutics for treating infections caused by multi-drug resistant bacteria is urgent. Staphylococcus aureus is a major human and animal pathogen, responsible for high levels of morbidity and mortality worldwide. The intracellular survival of S. aureus in macrophages contributes to immune evasion, dissemination, and resilience to antibiotic treatment. Here, we present a confocal fluorescence imaging assay for monitoring macrophage infection by green fluorescent protein (GFP)-tagged S. aureus as a front-line tool to identify antibiotic leads. The assay was employed in combination with nanoscaled chemical analyses to facilitate the discovery of a new, active rifamycin analogue. Our findings indicate a promising new approach for the identification of antimicrobial compounds with macrophage intracellular activity. The antibiotic identified here may represent a useful addition to our armory in tackling the silent pandemic of antimicrobial resistance.

Original languageEnglish
Pages (from-to)1499-1507
JournalACS infectious diseases
Volume9
Issue number8
Early online date11 Jul 2023
DOIs
Publication statusPublished - 11 Aug 2023

Keywords / Materials (for Non-textual outputs)

  • Animals
  • Anti-Bacterial Agents/pharmacology
  • Green Fluorescent Proteins/genetics
  • Humans
  • Macrophages
  • Rifamycins/therapeutic use
  • Staphylococcal Infections/microbiology
  • Staphylococcus aureus

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