Synergistic Activity of Colistin Combined With Auranofin Against Colistin-Resistant Gram-Negative Bacteria

Colistin-resistant (Col-R) bacteria are steadily increasing, and are extremely difficult to treat. New drugs or therapies are urgently needed to treat infections caused by these pathogens. Combination therapy with colistin and other old drugs, is an important way to restore the activity of colistin....

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Published inFrontiers in microbiology Vol. 12; p. 676414
Main Authors Feng, Xiaoxuan, Liu, Shuai, Wang, Yang, Zhang, Yulin, Sun, Lingxiao, Li, Haibo, Wang, Chunlei, Liu, Yingmei, Cao, Bin
Format Journal Article
LanguageEnglish
Published Frontiers Media S.A 25.06.2021
Subjects
auranofin
colistin
colistin-resistant
combination therapy
Microbiology
repurposing
synergistic effect
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Summary:Colistin-resistant (Col-R) bacteria are steadily increasing, and are extremely difficult to treat. New drugs or therapies are urgently needed to treat infections caused by these pathogens. Combination therapy with colistin and other old drugs, is an important way to restore the activity of colistin. This study aimed to investigate the activity of colistin in combination with the anti-rheumatic drug auranofin against Col-R Gram-negative bacteria. The results of checkerboard analysis demonstrated that auranofin synergized with colistin against Col-R Gram-negative bacteria. Time-kill assays showed significant synergistic antimicrobial activity of colistin combined with auranofin. Electron microscopy revealed that the combination resulted in more cellular structural alterations compared to each drug alone. Auranofin enhanced the therapeutic effectiveness of colistin in mouse peritoneal infection models. These results suggested that the combination of colistin and auranofin might be a potential alternative for the treatment of Col-R Gram-negative bacterial infections.
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Edited by: Haruyoshi Tomita, Gunma University, Japan
Reviewed by: Emanuele Durante Mangoni, University of Campania Luigi Vanvitelli, Italy; Younes Smani, Institute of Biomedicine of Seville (IBIS), Spain
This article was submitted to Antimicrobials, Resistance and Chemotherapy, a section of the journal Frontiers in Microbiology
ISSN:1664-302X
1664-302X
DOI:10.3389/fmicb.2021.676414