| Title: | Effects of an autoinducer analogue on antibiotic tolerance in Pseudomonas aeruginosa |
| Author(s): | Amoh T; Murakami K; Kariyama R; Hori K; Viducic D; Hirota K; Igarashi J; Suga H; Parsek MR; Kumon H; Miyake Y; |
| Address: | "Department of Oral Microbiology, Institute of Biomedical Sciences, Tokushima University Graduate School, 3-18-15 Kuramoto-cho, Tokushima 770-8504, Japan. Department of Urology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, 2-5-1 Shikata-cho, Okayama 700-8558, Japan. Department of Food and Nutrition, Okayama Gakuin University, 787 Aruki, Kurashiki, Okayama 710-0031, Japan. Innovation Center Okayama for Nanobio-targeted Therapy, Okayama University, 2-5-1 Shikata-cho, Okayama 700-8558, Japan. Discovery Research Lab., Otsuka Chemical Co. Ltd., 463, Kagasuno, Kawauchi, Tokushima 771-0193, Japan. Department of Chemistry, Graduate School of Science, the University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan. Department of Microbiology, University of Washington, 1959 NE Pacific St, Seattle, WA 98195, USA" |
| ISSN/ISBN: | 1460-2091 (Electronic) 0305-7453 (Print) 0305-7453 (Linking) |
| Abstract: | "OBJECTIVES: Antibiotic tolerance causes chronic, refractory and persistent infections. In order to advance the development of a new type of drug for the treatment of infectious diseases, we herein investigated the effects of a newly synthesized analogue of the Pseudomonas aeruginosa quorum-sensing autoinducer named AIA-1 ( a uto i nducer a nalogue) on antibiotic tolerance in P. aeruginosa . METHODS: A P. aeruginosa luminescent strain derived from PAO1 was injected into neutropenic ICR mice and bioluminescence images were acquired for a period of time after treatments with antibiotics and AIA-1. In vitro susceptibility testing and killing assays for the planktonic and biofilm cells of PAO1 were performed using antibiotics and AIA-1. The expression of quorum-sensing-related genes was examined using real-time PCR. RESULTS: In vivo and in vitro assays showed that AIA-1 alone did not exert any bactericidal effects and also did not affect the MICs of antibiotics. However, the combined use of AIA-1 and antibiotics exerted markedly stronger therapeutic effects against experimental infection than antibiotics alone. The presence of AIA-1 also enhanced the killing effects of antibiotics in planktonic and biofilm cells. Although AIA-1 did not inhibit the expression of lasB and rhlA genes, which are directly regulated by quorum sensing, it clearly suppressed expression of the rpoS gene. CONCLUSIONS: The new compound, AIA-1, did not alter the antibiotic susceptibility of P. aeruginosa by itself; however, its addition enhanced the antibacterial activity of antibiotics. AIA-1 did not inhibit quorum sensing, but reduced the antibiotic tolerance of P. aeruginosa by suppressing rpoS gene expression" |
| Keywords: | "Animals Anti-Bacterial Agents/*pharmacology *Drug Tolerance Mice, Inbred ICR Microbial Sensitivity Tests Microbial Viability/drug effects Pheromones/*metabolism Pseudomonas aeruginosa/*drug effects;" |
| Notes: | "MedlineAmoh, Takashi Murakami, Keiji Kariyama, Reiko Hori, Kenji Viducic, Darija Hirota, Katsuhiko Igarashi, Jun Suga, Hiroaki Parsek, Matthew R Kumon, Hiromi Miyake, Yoichiro eng R01 AI077628/AI/NIAID NIH HHS/ England 2017/05/17 J Antimicrob Chemother. 2017 Aug 1; 72(8):2230-2240. doi: 10.1093/jac/dkx132" |
