[Source: Journal of Infectious Diseases, full page. (LINK). Abstract, edited.]
Combination of Azithromycin and Gentamicin for Efficient Treatment of Pseudomonas aeruginosa Infections
Huan Ren, Yiwei Liu, Jingyi Zhou, Yuqing Long, Chang Liu, Bin Xia, Jing Shi, Zheng Fan,Yuying Liang, Shuiping Chen, Jun Xu, Penghua Wang, Yanhong Zhang, Guangbo Zhu,Huimin Liu, Yongxin Jin, Fang Bai, Zhihui Cheng, Shouguang Jin, Weihui Wu
The Journal of Infectious Diseases, jiz341, https://doi.org/10.1093/infdis/jiz341
Published: 16 August 2019
Trans-translation is a ribosome rescue system that plays an important role in bacterial tolerance to environmental stresses. It is absent in animals, making it a potential treatment target. However, its role in antibiotic tolerance in Pseudomonas aeruginosa remains unknown.
The role and activity of trans-translation during antibiotic treatment were examined with a trans-translation–deficient strain and a genetically modified trans-translation component gene, respectively. In vitro assays and murine infection models were used to examine the effects of suppression of trans-translation.
We found that the trans-translation system plays an essential role in P. aeruginosa tolerance to azithromycin and multiple aminoglycoside antibiotics. We further demonstrated that gentamicin could suppress the azithromycin-induced activation of trans-translation. Compared with each antibiotic individually, gentamicin and azithromycin combined increased the killing efficacy against planktonic and biofilm-associated P. aeruginosa cells, including a reference strain PA14 and its isogenic carbapenem-resistance oprD mutant, the mucoid strain FRD1, and multiple clinical isolates. Furthermore, the gentamicin-azithromycin resulted in improved bacterial clearance in murine acute pneumonia, biofilm implant, and cutaneous abscess infection models.
Combination treatment with gentamicin and azithromycin is a promising strategy in combating P. aeruginosa infections.
Pseudomonas aeruginosa, trans-translation, azithromycin, antibiotic combination
Topic: antibiotics – pseudomonas aeruginosa – gentamicin sulfate (usp) – azithromycin – biofilms – gentamicins – infection – killing
Issue Section: Major Article
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Keywords: Antibiotics; Drugs Resistance; Aminoglycosides; Gentamicin; Azithromycin; Pseudomonas aeruginosa; Biofilm.