A <i>Pseudomonas aeruginosa</i> Quorum-Sensing autoinducer analog enhances the activity of antibiotics against resistant strains

• Amoh Takashi

  Department of Oral Microbiology, Institute of Biomedical Sciences, Tokushima University Graduate School

• Murakami Keiji

  Department of Oral Microbiology, Institute of Biomedical Sciences, Tokushima University Graduate School

• Kariyama Reiko

  Department of Urology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Department of Food and Nutrition, Okayama Gakuin University

• Hori Kenji

  Innovation Center Okayama for Nanobio-targeted Therapy, Okayama University

• Irie Yasuhiko

  Department of Biology, University of Dayton

• Viducic Darija

  Department of Oral Microbiology, Institute of Biomedical Sciences, Tokushima University Graduate School

• Hirota Katsuhiko

  Department of Oral Microbiology, Institute of Biomedical Sciences, Tokushima University Graduate School

• Igarashi Jun

  Discovery Research Lab., Otsuka Chemical Co. Ltd.

• Suga Hiroaki

  Department of Chemistry, Graduate School of Science, the University of Tokyo

• Kumon Hiromi

  Department of Urology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University

• Miyake Yoichiro

  Department of Oral Microbiology, Institute of Biomedical Sciences, Tokushima University Graduate School

Abstract

In this study, we have investigated the effects of the newly synthesized analog of Pseudomonas aeruginosa quorum-sensing autoinducer named AIA-1 (autoinducer analog) against antibiotic-resistant bacteria. In vitro susceptibility and killing assays for P. aeruginosa PAO1ΔoprD mutant and clinical isolates were performed by using antibiotics and AIA-1. In an in vivo assay, a luminescent carbapenem-resistant strain derived from PAO1ΔoprD was injected into neutropenic ICR mice and bioluminescence images were acquired after the treatment with antibiotics and AIA-1. Additionally, we investigated the effects of the combination use against carbapenem-resistant Enterobacteriaceae (CRE). Using killing assays in P. aeruginosa, the survival rates in the presence of antibiotics and AIA-1 significantly decreased in comparison with those with antibiotics alone. Furthermore, dual treatment of biapenem and AIA-1 was more effective than biapenem alone in a mouse infection model. AIA-1 did not change the MICs in P. aeruginosa, suggesting that AIA-1 acts on the mechanism of antibiotic tolerance. Conversely, the MICs of antibiotics decreased in the presence of AIA-1 in some CRE strains, indicating that AIA-1 may require additional mechanism to act on CRE. In conclusion, AIA-1 may be a potent drug for clinical treatment of infections caused by antibiotic-resistant bacteria. J. Med. Invest. 64: 101-109, February, 2017

Journal

• The Journal of Medical Investigation

  The Journal of Medical Investigation 64 (1.2), 101-109, 2017

  The University of Tokushima Faculty of Medicine

Keywords

• Pseudomonas aeruginosa
• CRE
• antibiotic resistance

Details

• CRID: 1390282679222201728
• NII Article ID: 130005501959
• NII Book ID: AA11166929
• DOI: 10.2152/jmi.64.101
• ISSN: 13496867
• ISSN: 13431420
• PubMed: 28373605
• Web Site: https://www.jstage.jst.go.jp/article/jmi/64/1.2/64_101/_pdf
• Web Site: https://search.jamas.or.jp/link/ui/2018000315
• Text Lang: en
• Data Source:
  • JaLC
  • Crossref
  • PubMed
  • CiNii Articles
  • KAKEN
• Abstract License Flag: Disallowed