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188宝金博页面版: The antimicrobial peptide MPX kills Actinobacillus pleuropneumoniae and reduces its pathogenicity in mice.[2020][Vet Microbiol]

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内容提示: Contents lists available at ScienceDirectVeterinary Microbiologyjournal homepage: www.elsevier.com/locate/vetmicThe antimicrobial peptide MPX kills Actinobacillus pleuropneumoniae andreduces its pathogenicity in miceLei Wang a,c,1 , Xueqin Zhao a,b,1 , Chunling Zhu a , Yaya Zhao a , Shuangshuang Liu a , Xiaojing Xia a ,Xin Liu a , Huihui Zhang a , Yanzhao Xu a , Bolin Hang a , Yawei Sun a , Shijun Chen a , Jinqing Jiang a ,Yueyu Bai f , Gaiping Zhang c , Liancheng Lei d , Langford Paul Richard e , Hanna Fo...

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Contents lists available at ScienceDirectVeterinary Microbiologyjournal homepage: www.elsevier.com/locate/vetmicThe antimicrobial peptide MPX kills Actinobacillus pleuropneumoniae andreduces its pathogenicity in miceLei Wang a,c,1 , Xueqin Zhao a,b,1 , Chunling Zhu a , Yaya Zhao a , Shuangshuang Liu a , Xiaojing Xia a ,Xin Liu a , Huihui Zhang a , Yanzhao Xu a , Bolin Hang a , Yawei Sun a , Shijun Chen a , Jinqing Jiang a ,Yueyu Bai f , Gaiping Zhang c , Liancheng Lei d , Langford Paul Richard e , Hanna Fotina b, **,Jianhe Hu a, *a College of Animal Science and Veterinary Medicine, Henan Institute of Science and Technology, Xinxiang 453003, Chinab Faculty of Veterinary Medicine, Sumy National Agrarian University, Sumy, Ukrainec College of Animal Science and Veterinary Medicine, Henan Agricultural University, Zhengzhou 450000, Chinad College of Veterinary Medicine, JiLin University, Changchun 130000, Chinae Section of Paediatrics, Imperial College London, London, UKf Henan Breeding Cattle Genetic Properties Testing Center, Zhengzhou 450046, ChinaA R T I C L E I N F OKeywords:Antimicrobial peptide MPXActinobacillus pleuropneumoniaeBiof i lmLesionMiceA B S T R A C TActinobacillus pleuropneumoniae is the causative agent of highly contagious and fatal respiratory infections,causing substantial economic losses to the global pig industry. Due to increased antibiotic resistance, there is anurgent need to f i nd new antibiotic alternatives for treating A. pleuropneumoniae infections. MPX is obtained fromwasp venom and has a killing ef f ect on various bacteria. This study found that MPX had a good killing ef f ect onA. pleuropneumoniae and that the minimum inhibitory concentration (MIC) was 16 μg/mL. The bacterial densityof A. pleuropneumoniae decreased 1000 times after MPX (1 × MIC) treatment for 1 h, and the antibacterialactivity was not af f ected by pH or temperature. Fluorescence microscopy showed that MPX (1 × MIC) destroyedthe bacterial cell membrane after treatment for 0.5 h, increasing membrane permeability and releasing bacterialproteins and Ca 2+ , Na + and other cations. In addition, MPX (1 × MIC) treatment signif i cantly reduced theformation of bacterial biof i lms. Quantitative RT-PCR results showed that MPX treatment signif i cantly upregu-lated the expression of the PurC virulence gene and downregulated that of ApxI, ApxII, and Apa1. In addition,the Sap A gene was found to play an important role in the tolerance of A. pleuropneumoniae to antimicrobialpeptides. Therapeutic evaluation in a murine model showed that MPX protects mice from a lethal dose of A.pleuropneumoniae and relieves lung inf l ammation. This study reports the use of MPX to treat A. pleuropneumoniainfections, laying the foundation for the development of new drugs for bacterial infections.1. IntroductionActinobacillus pleuropneumoniae can colonise the upper and lowerrespiratory tracts of pigs, causing severe lung injury and leading topulmonary haemorrhage and necrosis; clinical features range fromacute to chronic (Chiers et al., 2010). A. pleuropneumoniae infection stillcauses serious economic losses to pig production worldwide. The clin-ical disease (if not treated) of A.pleuropneumoniae infection can cause a50 % increase in mortality (Hälli et al., 2014). There are 2 biotypes and18 serotypes of A. pleuropneumoniae, and each serotype produces atleast 2 extracellular toxins, which enhance the virulence and patho-genicity of A. pleuropneumoniae (Bosse et al., 2018). Due to the harmcaused by A. pleuropneumoniae, the treatment of A. pleuropneumoniaeinfections has become a research hotspot in recent years.With the long-term unreasonable use of antibiotics, antimicrobialresistance has become a global problem. Many pathogens are becomingmultidrug resistant with the attendant increased risk (Tillotson andZinner, 2017). Antimicrobial peptides are small-molecule active poly-peptides encoded by host genes that resist the invasion of pathogenicmicroorganisms and are an important part of the innate immunehttps://doi.org/10.1016/j.vetmic.2020.108634Received 13 August 2019; Received in revised form 22 February 2020; Accepted 2 March 2020? Corresponding author at: College of Animal Science and Veterinary Medicine, Henan Institute of Science and Technology, Xinxiang, P. R. China.?? Corresponding author at: Faculty of Veterinary Medicine, Sumy National Agrarian University, Sumy, Ukraine.E-mail addresses: jianhehu@126.com (J. Hu), super.annafotina@ukr.net (H. Fotina).1 Lei Wang and Xueqin Zhao contributed equally to this work and share f i rst authorship.Veterinary Microbiology 243 (2020) 1086340378-1135/ © 2020 Elsevier B.V. All rights reserved.T

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