Effect of Sub-MICs of Macrolides on the Sensitivity of Pseudomonas aeruginosa to Nitrosative Stress: Effectiveness against P. aeruginosa with and without Multidrug Resistance

Takeshi Shimizu; Tohru Miyoshi-Akiyama; Kohei Ogura; Shota Murata; Shota Ishige; Kiyohiro Kai; Konosuke Mitsutsuka; Haruyoshi Tomita; Koichi Tanimoto; Akio Matsumoto

doi:10.1128/AAC.01180-20

Effect of Sub-MICs of Macrolides on the Sensitivity of Pseudomonas aeruginosa to Nitrosative Stress: Effectiveness against P. aeruginosa with and without Multidrug Resistance

Antimicrob Agents Chemother. 2020 Sep 21;64(10):e01180-20. doi: 10.1128/AAC.01180-20. Print 2020 Sep 21.

Authors

Affiliations

¹ Department of Molecular Infectiology, Graduate School of Medicine, Chiba University, Chiba, Japan tshimizu@faculty.chiba-u.jp.
² Pathogenic Microbe Laboratory, Research Institute, National Center for Global Health and Medicine, Tokyo, Japan.
³ Advanced Health Care Science Research Unit, Institute for Frontier Science Initiative, Kanazawa University, Kanazawa, Ishikawa, Japan.
⁴ Division of Laboratory Medicine, Chiba University Hospital, Chiba, Japan.
⁵ Department of Molecular Infectiology, Graduate School of Medicine, Chiba University, Chiba, Japan.
⁶ Department of Bacteriology, Graduate School of Medicine, Gunma University, Maebashi, Gunma, Japan.
⁷ Laboratory of Bacterial Drug Resistance, Graduate School of Medicine, Gunma University, Maebashi, Gunma, Japan.
⁸ Department of Aging Pharmacology, Faculty of Medicine, Toho University, Tokyo, Japan.

Abstract

Sub-MICs of the 14-membered macrolides erythromycin (EM) and clarithromycin (CAM) decreased the growth of Pseudomonas aeruginosa PAO1 and increased its sensitivity to endogenous and exogenous nitrosative stress. However, a 16-membered macrolide, josamycin (JM), was not or less effective. In 9 of 13 non-multidrug-resistant P. aeruginosa (non-MDRP) and 9 of 27 MDRP ST235 strains, the sub-MIC of EM induced significant reductions in bacterial numbers following treatment with a nitric oxide donor.

Keywords: Pseudomonas aeruginosa; ST235; biofilm; macrolide; multidrug-resistant P. aeruginosa; nitric oxide.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Anti-Bacterial Agents / pharmacology
Drug Resistance, Multiple
Macrolides* / pharmacology
Microbial Sensitivity Tests
Nitrosative Stress
Pseudomonas aeruginosa*

Substances

Anti-Bacterial Agents
Macrolides