title: A Pseudomonas aeruginosa Quorum-Sensing autoinducer analog enhances the activity of antibiotics against resistant strains.
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.
authors.affiliation: Department of Oral Microbiology, Institute of Biomedical Sciences, Tokushima University Graduate School.
authors.forename: Takashi
authors.initials: T
authors.lastname: Amoh
authors.forename: Keiji
authors.initials: K
authors.lastname: Murakami
authors.forename: Reiko
authors.initials: R
authors.lastname: Kariyama
authors.forename: Kenji
authors.initials: K
authors.lastname: Hori
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Irie
authors.forename: Darija
authors.initials: D
authors.lastname: Viducic
authors.forename: Katsuhiko
authors.initials: K
authors.lastname: Hirota
authors.forename: Jun
authors.initials: J
authors.lastname: Igarashi
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Suga
authors.forename: Hiromi
authors.initials: H
authors.lastname: Kumon
authors.forename: Yoichiro
authors.initials: Y
authors.lastname: Miyake
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage*; D015780:Carbapenems / Q000494:pharmacology; D004357:Drug Synergism; D006714:Homoserine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry; D006801:Humans; D007783:Lactones / Q000008:administration & dosage* / Q000138:chemical synthesis / Q000737:chemistry; D051379:Mice; D008813:Mice, Inbred ICR; D011552:Pseudomonas Infections / Q000188:drug therapy / Q000382:microbiology; D011550:Pseudomonas aeruginosa / Q000187:drug effects* / Q000235:genetics; D053038:Quorum Sensing / Q000187:drug effects; D013845:Thienamycins / Q000008:administration & dosage; D018440:beta-Lactam Resistance
chemical_list: D000900:Anti-Bacterial Agents; D015780:Carbapenems; D007783:Lactones; D013845:Thienamycins; C085113:Pseudomonas aeruginosa autoinducer; D006714:Homoserine; C065257:biapenem