Riccardin C derivatives cause cell leakage in Staphylococcus aureus

Daichi Morita, Hiromi Sawada, Wakano Ogawa, Hiroyuki Miyachi, Teruo Kuroda

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Methicillin-resistant Staphylococcus aureus (MRSA) is a major problem in clinical settings, and because it is resistant to most antimicrobial agents, MRSA infections are difficult to treat. We previously reported that synthetic macrocyclic bis(bibenzyl) derivatives, which were originally discovered in liverworts, had anti-MRSA activity. However, the action mechanism responsible was unclear. In the present study, we elucidated the action mechanism of macrocyclic bis(bibenzyl) RC-112 and its partial structure, IDPO-9 (2-phenoxyphenol). Survival experiments demonstrated that RC-112 had a bactericidal effect on MRSA, whereas IDPO-9 had bacteriostatic effects. IDPO-9-resistant mutants exhibited cross-resistance to triclosan, but not to RC-112. The mutation was identified in the fabI, enoyl-acyl carrier protein reductase gene, a target of triclosan. We have not yet isolated the RC-112-resistant mutant. On the other hand, the addition of RC-112, unlike IDPO-9, caused the inflow of ethidium and propidium into S. aureus cells. RC-112-dependent ethidium outflow was observed in ethidium-loaded S. aureus cells. Transmission electron microscopy also revealed that S. aureus cells treated with RC-112 had intracellular lamellar mesosomal-like structures. Intracellular Na+ and K+ concentrations were significantly changed by the RC-112 treatment. These results indicated that RC-112 increased membrane permeability to ethidium, propidium, Na+, and K+, and also that the action mechanism of IDPO-9 was different from those of the other compounds.

Original languageEnglish
Pages (from-to)2057-2064
Number of pages8
JournalBBA - Biomembranes
Volume1848
Issue number10
DOIs
Publication statusPublished - Jul 11 2015

Fingerprint

Methicillin
Ethidium
Methicillin-Resistant Staphylococcus aureus
Staphylococcus aureus
Triclosan
Derivatives
Propidium
Hepatophyta
Acyl Carrier Protein
Anti-Infective Agents
Transmission Electron Microscopy
Permeability
Oxidoreductases
Genes
Transmission electron microscopy
Membranes
Mutation
riccardin C
Infection
Experiments

Keywords

  • Cell leakage
  • Macrocyclic bis(bibenzyl)
  • Mesosome
  • MRSA
  • Riccardin C

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Biophysics
  • Medicine(all)

Cite this

Morita, D., Sawada, H., Ogawa, W., Miyachi, H., & Kuroda, T. (2015). Riccardin C derivatives cause cell leakage in Staphylococcus aureus. BBA - Biomembranes, 1848(10), 2057-2064. https://doi.org/10.1016/j.bbamem.2015.05.008

Riccardin C derivatives cause cell leakage in Staphylococcus aureus. / Morita, Daichi; Sawada, Hiromi; Ogawa, Wakano; Miyachi, Hiroyuki; Kuroda, Teruo.

In: BBA - Biomembranes, Vol. 1848, No. 10, 11.07.2015, p. 2057-2064.

Research output: Contribution to journalArticle

Morita, D, Sawada, H, Ogawa, W, Miyachi, H & Kuroda, T 2015, 'Riccardin C derivatives cause cell leakage in Staphylococcus aureus', BBA - Biomembranes, vol. 1848, no. 10, pp. 2057-2064. https://doi.org/10.1016/j.bbamem.2015.05.008
Morita D, Sawada H, Ogawa W, Miyachi H, Kuroda T. Riccardin C derivatives cause cell leakage in Staphylococcus aureus. BBA - Biomembranes. 2015 Jul 11;1848(10):2057-2064. https://doi.org/10.1016/j.bbamem.2015.05.008
Morita, Daichi ; Sawada, Hiromi ; Ogawa, Wakano ; Miyachi, Hiroyuki ; Kuroda, Teruo. / Riccardin C derivatives cause cell leakage in Staphylococcus aureus. In: BBA - Biomembranes. 2015 ; Vol. 1848, No. 10. pp. 2057-2064.
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