Next Article in Journal
Gd-Complexes of New Arylpiperazinyl Conjugates of DTPA-Bis(amides): Synthesis, Characterization and Magnetic Relaxation Properties
Next Article in Special Issue
Assessing the Chemical Composition and Antimicrobial Activity of Essential Oils from Brazilian Plants—Eremanthus erythropappus (Asteraceae), Plectrantuns barbatus, and P. amboinicus (Lamiaceae)
Previous Article in Journal
Riluzole as a Neuroprotective Drug for Spinal Cord Injury: From Bench to Bedside
Previous Article in Special Issue
A Facile Synthesis and Antimicrobial Activity Evaluation of Sydnonyl-Substituted Thiazolidine Derivatives
Open AccessArticle

Development of a Novel Antimicrobial Screening System Targeting the Pyoverdine-Mediated Iron Acquisition System and Xenobiotic Efflux Pumps

Laboratory of Animal Microbiology, Department of Microbial Biotechnology, Graduate School of Agricultural Science, Tohoku University, 1-1 Tsutsumidori, Amamiya-machi, Aoba-ku, Sendai 981-8555, Japan
Institute of Scientific and Industrial Research, Osaka University, Ibaraki, Osaka 567-0047, Japan
Department of Biological Science and Technology, Faculty of Engineering, 2-1 Minamijyousanjima-cho, Tokushima 770-8605, Japan
Laboratory for Antimicrobial Agents, Kitasato University, 1-15-1 Kitasato, Sagamihara 228-8555, Japan
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Academic Editor: Peter J. Rutledge
Molecules 2015, 20(5), 7790-7806;
Received: 9 February 2015 / Revised: 19 March 2015 / Accepted: 23 April 2015 / Published: 29 April 2015
The iron acquisition systems in Pseudomonas aeruginosa are inducible in response to low-iron conditions and important for growth of this organism under iron limitation. OprM is the essential outer membrane subunit of the MexAB-OprM xenobiotic efflux pump. We designed and constructed a new model antimicrobial screening system targeting both the iron-uptake system and xenobiotic efflux pumps. The oprM gene was placed immediately downstream of the ferri-pyoverdine receptor gene, fpvA, in the host lacking chromosomal oprM and the expression of oprM was monitored by an antibiotic susceptibility test under iron depleted and replete conditions. The recombinant cells showed wild-type susceptibility to pump substrate antibiotics, e.g., aztreonam, under iron limitation and became supersusceptible to them under iron repletion, suggesting that expression of oprM is under control of the iron acquisition system. Upon screening of a chemical library comprising 2952 compounds using this strain, a compound—ethyl 2-(1-acetylpiperidine-4-carboxamido)-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate—was found to enhance the efficacy of aztreonam under iron limitation, suggesting that the compound inhibits either the iron acquisition system or the MexAB-OprM efflux pump. This compound was subsequently found to inhibit the growth of wild-type cells in the presence of sublethal amounts of aztreonam, regardless of the presence or absence of dipyridyl, an iron-chelator. The compound was eventually identified to block the function of the MexAB-OprM efflux pump, showing the validity of this new method. View Full-Text
Keywords: antimicrobials; iron acquisition systems; efflux pumps; Pseudomonas aeruginosa antimicrobials; iron acquisition systems; efflux pumps; Pseudomonas aeruginosa
Show Figures

Graphical abstract

MDPI and ACS Style

Sato, K.; Ushioda, K.; Akiba, K.; Matsumoto, Y.; Maseda, H.; Ando, T.; Isogai, E.; Nakae, T.; Yoneyama, H. Development of a Novel Antimicrobial Screening System Targeting the Pyoverdine-Mediated Iron Acquisition System and Xenobiotic Efflux Pumps. Molecules 2015, 20, 7790-7806.

Show more citation formats Show less citations formats

Article Access Map by Country/Region

Only visits after 24 November 2015 are recorded.
Back to TopTop