alexa Exposure to Reactive Oxygen Species and Piperacillin Leads to Multidrug Resistance in Pseudomonas aeruginosa PAO1 | OMICS International | Abstract
ISSN: 2327-5073

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Research Article

Exposure to Reactive Oxygen Species and Piperacillin Leads to Multidrug Resistance in Pseudomonas aeruginosa PAO1

Sachiko Hayakawa1,2*, Emiko Furukawa1, Masato Kawamura1, Toshiaki Kikuchi3, Taizou Hirano4, Akira Watanabe5 and Shigeru Fujimura1,5

1Division of Clinical Infectious Disease & Chemotherapy, Tohoku Medical and Pharmaceutical University, Sendai, Japan

2Department of Pharmacy, Tohoku Medical and Pharmaceutical University Hospital, Sendai, Japan

3Department of Respiratory Medicine and Infectious Diseases, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan

4Department of Respiratory, Tohoku University Graduate School of Medicine, Sendai, Japan

5Resarch Division of Development of Anti-Infective Agents, Institute of Development Aging and Cancer, Tohoku University, Sendai, Japan

*Corresponding Author:
Sachiko Hayakawa
Division of Clinical Infectious Disease & Chemotherapy
Tohoku Medical and Pharmaceutical University, Sendai, Japan
Tel: +81-22-259-1221
Fax: +81-22-259-1232
E-mail: [email protected]

Received date: October 15, 2016; Accepted date: October 31, 2016; Published date: November 20, 2016

Citation: Hayakawa S, Furukawa E, Kawamura M, Kikuchi T, Hirano T, et al. (2016) Exposure to Reactive Oxygen Species and Piperacillin Leads to Multidrug Resistance in Pseudomonas aeruginosa PAO1. Clin Microbiol 5:264. doi: 10.4172/2327-5073.1000264

Copyright: © 2016 Hayakawa S, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


Pseudomonas aeruginosa is one of the most common causes of nosocomial infections. Hospital associated infection by multidrug resistant (MDR) strains constitute a serious problem worldwide. The aim of the present study was to evaluate whether exposure to sub-MIC levels of anti-pseudomonas antibiotics and reactive oxygen species (ROS), such as hydroxyl radicals, could lead to MDR of P. aeruginosa. P. aeruginosa standard strain PAO1 was used in this study. All five anti-pseudomonas agents, that is, piperacillin, levofloxacin, meropenem, ceftazidime and amikacin, were investigated for induction of resistance and cross-resistance in vitro. The reference strain was incubated 24 h and transferred 5 times after being exposed to 1 mM H2O2 in addition to a sub-MIC of each antibiotic by the agar dilution method. When cross-resistance to another antibiotic was confirmed, ampC, mexAB, and oprD expression and mutation of QRDR were investigated. Sub-MIC of piperacillin induced resistance to piperacillin and levofloxacin under stimulation with ROS. The mechanism of multi-resistance to β-lactams and levofloxacin was confirmed by RT-PCR. It was a decrease of oprD expression (p<0.05). The increase of MIC was inhibited by the ROS scavenger sodium zinc histidine dihydrolipoyl histidinate (DHL-His-Zn). In conclusion, for P. aeruginosa PAO1 to acquire multidrug resistance, stimulation with ROS was as important as exposure to sub-MIC of piperacillin.


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