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Furazolidone reduces the pathogenesis of Trueperella pyogenes and Pseudomonas aeruginosa co-infection in a mouse model

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机构： [1]Key Laboratory of Qinghai-Tibetan Plateau Animal Genetic Resource Reservation and Utilization, Sichuan Province and Ministry of Education, Southwest Minzu University, Chengdu, 610225, China. [2]Sichuan Key Laboratory of Conservation Biology on Endangered Wildlife, College of Life Sciences, Sichuan University, Chengdu, 610064, China. [3]Antibiotics Research and Re-evaluation Key Laboratory of Sichuan Province, School of Pharmacy, Chengdu University, Chengdu, 610106, China. [4]State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, 610041, China. [5]Institute for Advanced Study, Chengdu University, Chengdu, 610106, China.

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关键词： Abscess disease Furazolidone Quorum sensing anti-virulence mouse model

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The prevalence of abscess disease significantly limits the population expansion of captive forest musk deer, which is an endangered species protected by the legislation of China. Our prior work had demonstrated that Trueperella pyogenes and Pseudomonas aeruginosa are two important microorganisms in causing the abscess disease of forest musk deer, and furazolidone could inhibit the growth and virulence of the pathogens in vitro. In this study, the in vivo protection activity of furazolidone was evaluated by using mouse models chronically infected with T. pyogenes and P. aeruginosa. The results showed that furazolidone treatment significantly increased the survival rates of mice in the co-infection group, all the mice survived at 14 days post-infection. The damage degree of the lung tissues caused by bacterial infection was ameliorated by the treatment of furazolidone from 7 to 14 days post-infection, which also reduced the residual bacterial burden in the lungs. Compared to the untreated control group, the expression levels of genes activated by the quorum-sensing system of P. aeruginosa and the core virulence regulatory genes of T. pyogenes were significantly suppressed by furazolidone. In addition, the results of transcriptomic analyses showed that 270 DEGs were identified in the co-infection group. This finding further revealed that the immune responses of mice could be enhanced by the treatment of furazolidone, and this might also contribute to the clearance of bacteria from the lungs. Therefore, this study clearly reveals the protection activity of furazolidone against P. aeruginosa and T. pyogenes infection, and thus provides a promising candidate in the treatment of abscess disease.© 2024 The Authors.

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大类 | 3 区综合性期刊

小类 | 3 区综合性期刊

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第一作者机构： [1]Key Laboratory of Qinghai-Tibetan Plateau Animal Genetic Resource Reservation and Utilization, Sichuan Province and Ministry of Education, Southwest Minzu University, Chengdu, 610225, China.

通讯作者：

通讯机构： [3]Antibiotics Research and Re-evaluation Key Laboratory of Sichuan Province, School of Pharmacy, Chengdu University, Chengdu, 610106, China. [5]Institute for Advanced Study, Chengdu University, Chengdu, 610106, China.

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