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Prostaglandins Leukot Essent Fatty Acids. 2018 Jun;133:16-22. doi: 10.1016/j.plefa.2018.04.005. Epub 2018 Apr 26.

Prostaglandin E2 attenuates synergistic bactericidal effects between COX inhibitors and antibiotics on Staphylococcus aureus.

Author information

1
China-Japan Research Institute of Medical and Pharmaceutical Sciences, Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang 110016, China. Electronic address: caijiayi2008yy@163.com.
2
China-Japan Research Institute of Medical and Pharmaceutical Sciences, Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang 110016, China. Electronic address: 15542155696@163.com.
3
China-Japan Research Institute of Medical and Pharmaceutical Sciences, Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang 110016, China. Electronic address: 18842538590@163.com.
4
China-Japan Research Institute of Medical and Pharmaceutical Sciences, Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang 110016, China. Electronic address: mkarthas@163.com.
5
School of Traditional Chinese Materia Medica, Key Laboratory of Structure-Based Drug Design & Discovery (Ministry of Education), Shenyang Pharmaceutical University, Shenyang 110016, China. Electronic address: guodong_yao@126.com.
6
China-Japan Research Institute of Medical and Pharmaceutical Sciences, Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang 110016, China. Electronic address: lww0206@126.com.
7
China-Japan Research Institute of Medical and Pharmaceutical Sciences, Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang 110016, China. Electronic address: toshihikohayashi@vip.sina.com.
8
Biotechnical Center, Japan SLC, Inc., Shizuoka 431-1103, Japan. Electronic address: kitoh@fj8.so-net.jp.
9
Department of Medical Education & Primary Care, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan. Electronic address: tassprof@gmail.com.
10
Department of Clinical and Pharmaceutical Sciences, Showa Pharmaceutical University, Tokyo 194-8543, Japan. Electronic address: onodera@ac.shoyaku.ac.jp.
11
China-Japan Research Institute of Medical and Pharmaceutical Sciences, Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang 110016, China. Electronic address: ikejimat@vip.sina.com.

Abstract

PGE2 is found to attenuate the bactericidal effects of kanamycin or ampicillin in Staphylococcus aureus, as well as the methicillin-resistant S. aureus (MRSA). Co-treatment with cyclooxygenase (COX) inhibitors (celecoxib, aspirin or naproxen) synergistically enhances kanamycin or ampicillin-induced cell death of S. aureus and MRSA. COX inhibitors repressed bacterial multidrug resistance through down-regulating efflux pump activity in antibiotics-treated S. aureus and MRSA. However, this synergistic bactericidal effects are reduced by the treatment with PGE2. PGE2 restores the efflux pump activity as well as increases biofilm formation in S. aureus and MRSA. Collectively, the enhancement of efflux pump activity and biofilm formation with PGE2 might partially explain the resistance to synergistic bactericidal effects between COX inhibitors and antibiotics in PGE2-treated S. aureus.

KEYWORDS:

Antibiotic; Biofilm formation; COX inhibitors; Efflux pump; Prostaglandin E2

PMID:
29789128
DOI:
10.1016/j.plefa.2018.04.005
[Indexed for MEDLINE]

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