Furazolidone reduces the pathogenesis of Trueperella pyogenes and Pseudomonas aeruginosa co-infection in a mouse model
Nan Yang,
Heyue Li,
Xiting Yang,
Yi Wu,
Zheng Lv,
Ziheng Zhang,
Xiaoling Ma,
Xikun Zhou,
Xiuyue Zhang,
Kelei Zhao,
Lianming Du,
Ting Huang
Affiliations
Nan Yang
Key Laboratory of Qinghai-Tibetan Plateau Animal Genetic Resource Reservation and Utilization, Sichuan Province and Ministry of Education, Southwest Minzu University, Chengdu, 610225, China
Heyue Li
Sichuan Key Laboratory of Conservation Biology on Endangered Wildlife, College of Life Sciences, Sichuan University, Chengdu, 610064, China
Xiting Yang
Antibiotics Research and Re-evaluation Key Laboratory of Sichuan Province, School of Pharmacy, Chengdu University, Chengdu, 610106, China
Yi Wu
Antibiotics Research and Re-evaluation Key Laboratory of Sichuan Province, School of Pharmacy, Chengdu University, Chengdu, 610106, China
Zheng Lv
Antibiotics Research and Re-evaluation Key Laboratory of Sichuan Province, School of Pharmacy, Chengdu University, Chengdu, 610106, China
Ziheng Zhang
Antibiotics Research and Re-evaluation Key Laboratory of Sichuan Province, School of Pharmacy, Chengdu University, Chengdu, 610106, China
Xiaoling Ma
Antibiotics Research and Re-evaluation Key Laboratory of Sichuan Province, School of Pharmacy, Chengdu University, Chengdu, 610106, China
Xikun Zhou
State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, 610041, China
Xiuyue Zhang
Sichuan Key Laboratory of Conservation Biology on Endangered Wildlife, College of Life Sciences, Sichuan University, Chengdu, 610064, China
Kelei Zhao
Antibiotics Research and Re-evaluation Key Laboratory of Sichuan Province, School of Pharmacy, Chengdu University, Chengdu, 610106, China
Lianming Du
Antibiotics Research and Re-evaluation Key Laboratory of Sichuan Province, School of Pharmacy, Chengdu University, Chengdu, 610106, China; Institute for Advanced Study, Chengdu University, Chengdu, 610106, China; Corresponding author. Antibiotics Research and Re-evaluation Key Laboratory of Sichuan Province, School of Pharmacy, Chengdu University, Chengdu, 610106, China.
Ting Huang
Antibiotics Research and Re-evaluation Key Laboratory of Sichuan Province, School of Pharmacy, Chengdu University, Chengdu, 610106, China; Corresponding author. No. 2025, Chengluo Avenue, Chengdu, 610106, Sichuan, China.
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.
