异丙氧苯胍与黏菌素联用对多杀性巴氏杆菌的体内外抗菌作用

doi:10.16431/j.cnki.1671-7236.2024.02.038

Abstract

Abstract: 【Objective】 This study was aimed to investigate the antibacterial effect of isopropoxy benzene guanidine (IBG) with colistin against Pasteurella multocida (P.multocida) in vivo and in vitro, in order to provide data support for the development of effective new colistin synergists and clinical prevention and treatment of P.multocida.【Method】 The minimum inhibitory concentration of IBG and colistin was determined by broth microdilution.The in vitro antibacterial activity against P.multocida was evaluated by checkerboard assays and time-kill curves, and the in vivo antibacterial effect was further evaluated by establishing a mouse lung infection model.【Result】 The drug sensitivity test results showed that IBG had no antibacterial effect on P.multocida (MIC＞256 μg/mL), the MIC range of colistin on the tested P.multocida strains was 1-8 μg/mL.When IBG was combined with colistin, it could enhance the antibacterial activity of colistin (FIC was 0.094-0.313), demonstrating an excellent synergistic antibacterial effect.The time-kill curves further indicated that the combination group could significantly reduce the number of bacteria.The bactericidal effect could be achieved when colistin with sub inhibitory concentration (0.5 μg/mL) was combined with IBG.In the mouse lung infection model, the combination group could significantly or extremely significantly reduce the bacterial burden of P.multocida in lungs compared to the colistin or IBG alone group (P＜0.05 or P＜0.01).The pathological tissue sections of mouse lungs showed that the alveolar structure was normal and the alveolar cavities were clean in the combined group, which was better than IBG and colistin alone.【Conclusion】 The combination of IBG and colistin could enhance the antibacterial effect of colistin against P.multocida in vivo and in vitro, and was expected to be further developed as a new antibacterial synergist.

Key words: isopropoxy benzene guanidine; colistin; combined medication; Pasteurella multocida; antibacterial effect

CLC Number:

S859.7

XUE Yaqian, QIAO Weimei, HONG Xiaoxin, JIN Yuhang, LU Yixing, PENG Xianfeng, ZENG Zhenling. In vitro and in vivo Antibacterial Effect of Isopropoxy Benzene Guanidine Combined with Colistin Against Pasteurella multocida[J]. China Animal Husbandry and Veterinary Medicine, 2024, 51(2): 820-828.

References

[1] 陆承平.兽医微生物学[M].5版.北京:中国农业出版社,2013. LU C P.Veterinary Microbiology[M].5th ed.Beijing:China Agriculture Press,2013.(in Chinese)
[2] WILKIE I W,HARPER M,BOYCE J D,et al.Pasteurella multocida:Diseases and pathogenesis[J].Current Topics in Microbiology and Immunology,2012,361:1-22.
[3] WILSON B A,HO M.Pasteurella multocida:From zoonosis to cellular microbiology[J].Clinical Microbiology Reviews,2013,26(3):631-655.
[4] 赵梦坡,朱志森,黄育浩,等.多杀性巴氏杆菌疫苗研究进展[J].广东畜牧兽医科技,2022,47(6):45-51. ZHAO M P,ZHU Z S,HUANG Y H,et al.Research progress on Pasteurella multocida vaccine[J].Guangdong Journal of Animal and Veterinary Science,2022,47(6):45-51.(in Chinese)
[5] 黄忍,张定练,肖驰.贵州部分地区规模猪场链球菌和多杀性巴氏杆菌的耐药性分析[J].饲料博览,2022,6:73-76. HUANG R,ZHANG D L,XIAO C.Drug resistance analysis of Streptococcus suis and Pasteurella multocida on large-scale pig farms in some areas of Guizhou province[J].Feed Review,2022,6:73-76.(in Chinese)
[6] 邹本革,张伟,张瑞华,等.猪源多杀性巴氏杆菌的分离鉴定及耐药性分析[J].中国兽医杂志,2022,58(7):90-96. ZOU B G,ZHANG W,ZHANG R H,et al.Isolation,identification and drug resistance analysis of Pasteurella multocida from swine[J]. Chinese Journal of Veterinary Medicine,2022,58(7):90-96.(in Chinese)
[7] 张亚楠,李亚菲,陈汝佳,等.A:L1 ST128型鸭源多杀性巴氏杆菌的耐药性及毒力分析[J].畜牧兽医学报,2021,52(10):2852-2863. ZHANG Y N,LI Y F,CHEN R J,et al.Resistance and virulence analysis of type A:L1 ST128Pasteurella multocida from ducks[J].Acta Veterinaria et Zootechnica Sinica,2021,52(10):2852-2863.(in Chinese)
[8] 刘海燕,杨有文,王远微,等.6株山羊源多杀性巴氏杆菌血清型、耐药性及致病性分析[J].黑龙江畜牧兽医,2020,16:65-68. LIU H Y,YANG Y W,WANG Y W,et al.Serotype,drug resistance and pathogenicity of six Pasteurella multocida strains from goats[J].Heilongjiang Animal Science and Veterinary Medicine,2020,16:65-68.(in Chinese)
[9] 陈杖榴,曾振灵.兽医药理学[M].4版.北京:中国农业出版社,2017. CHEN Z L,ZENG Z L.Veterinary Pharmacology[M].4th ed.Beijing:China Agriculture Press,2017.(in Chinese)
[10] AYOUB M C.Polymyxins and bacterial membranes:A review of antibacterial activity and mechanisms of resistance[J].Membranes (Basel),2020,10(8):181.
[11] 胡功政,崔小蝶,翟亚军,等.细菌黏菌素耐药性及其逆转机制研究进展[J].生物技术通报,2022,38(9):28-34. HU G Z,CUI X D,ZHAI Y J,et al.Research progress in colistin (COL) resistance in bacterial and its reversal mechanism[J].Biotechnology Bulletin,2022,38(9):28-34.(in Chinese)
[12] 王莹,卢葛锦,景洁,等.畜禽源耐黏菌素大肠埃希氏菌的分离鉴定与特性分析[J].动物医学进展,2022,43(11):27-33. WANG Y,LU G J,JING J,et al.Isolation,identification and characterization of colistin resistant Escherichia coli from livestock and poultry[J].Progress in Veterinary Medicine,2022,43(11):27-33.(in Chinese)
[13] LIU Y Y,WANG Y,WALSH T R,et al.Emergence of plasmid-mediated colistin resistance mechanism MCR-1 in animals and human beings in China:A microbiological and molecular biological study[J].Lancet Infectious Diseases,2016,16(2):161-168.
[14] KAPP T G,FOTTNER M,KESSLER H.Modification and functionalization of the guanidine group by tailor-made precursors[J].Jove-Journal of Visualized Experiments,2017,122:e54873.
[15] SACZEWSKI F,BALEWSKI A.Biological activities of guanidine compounds,2008-2012 update[J].Expert Opinion on Therapeutic Patents,2013,23(8):965-995.
[16] ZHANG X,HAN D,PEI P,et al.In vitro antibacterial activity of isopropoxy benzene guanidine against multidrug-resistant enterococci[J].Infection and Drug Resistance,2019,12:3943-3953.
[17] ZHANG X,XIONG W,PENG X,et al.Isopropoxy benzene guanidine kills Staphylococcus aureus without detectable resistance[J].Frontiers in Microbiology,2021,12:633467.
[18] LU Y,YANG L,ZHANG W,et al.Pharmacokinetics and pharmacodynamics of isopropoxy benzene guanidine against Clostridium perfringens in an intestinal infection model[J].Frontiers in Veterinary Science,2022,9:1004248.
[19] HAN N,LI J,ZHAO F,et al.Isopropoxy benzene guanidine ameliorates Streptococcus suis infection in vivo and in vitro[J].International Journal of Molecular Science,2023,24(8):7354.
[20] 张秀凤.异丙氧苯胍对金黄色葡萄球菌和大肠杆菌的抗菌作用及其机制研究[D].广州:华南农业大学,2020. ZHANG X F.Study on antibacterial effect and mechanism of isopropoxy benzene guanidine against Staphylococcus aureus and Escherichia coli[D].Guangzhou:South China Agricultural University,2020.(in Chinese)
[21] KONG L,LU Y,YANG L,et al.Pharmacokinetics and pharmacodynamics of colistin combined with isopropoxy benzene guanidine against mcr-1-positive Salmonella in an intestinal infection model[J].Frontiers in Microbiology,2022,13:907116.
[22] ODDS F C.Synergy,antagonism,and what the chequerboard puts between them[J].Journal of Antimicrobial Chemotherapy,2003,52(1):1.
[23] 李静,杨靖亚,杨怡,等.联合用药:未来抗菌药物研发的趋势[J].中国抗生素杂志,2021,46(7):633-637. LI J,YANG J Y,YANG Y,et al.Drug combinations:The research trend of antibiotics in the future[J].Chinese Journal of Antibiotics,2021,46(7):633-637.(in Chinese)
[24] 郭伟娜,赵霞,路振香.兔源多杀性巴氏杆菌的分离鉴定及耐药性分析[J].中国兽医杂志,2023,59(4):59-62. GUO W N,ZHAO X,LU Z X.Isolation,identification and drug resistance analysis of Pasteurella multocida from rabbits[J].Chinese Journal of Veterinary Medicine,2023,59(4):59-62.(in Chinese)
[25] 王喜,元正菊,张信艳,等.鸡源多杀性巴氏杆菌的分离鉴定及生物学特性分析[J].中国兽医科学,2021,51(11):1411-1419. WANG X,YUAN Z J,ZHANG X Y,et al.Isolation,identification and biological characteristic analysis of Pasteurella multocida from chicken[J].Chinese Veterinary Science,2021,51(11):1411-1419.(in Chinese)
[26] 毛畅思,党乔,魏星,等.牛多杀性巴氏杆菌的分离鉴定与药敏试验[J].动物医学进展,2021,42(1):46-50. MAO C S,DANG Q,WEI X,et al.Isolation,identification and drug sensitivity test of Pasteurella multocida in cattle[J].Progress in Veterinary Medicine,2021,42(1):46-50.(in Chinese)
[27] 陈国权,张旭,阎朝华,等.鸭源多杀性巴氏杆菌的分离鉴定及耐药性分析[J].中国畜牧兽医, 2020,47(2):620-628. CHEN G Q,ZHANG X,YAN C H,et al.Isolation,identification and drug resistance analysis of Pasteurella multocida from ducks[J]. China Animal Husbandry&Veterinary Medicine,2020,47(2):620-628.(in Chinese)
[28] 孙灵灵,袁宗辉,李梅,等.抗菌增效剂药动学与残留消除研究进展[J].中国畜牧兽医,2016,43(12):3141-3148. SUN L L,YUAN Z H,LI M,et al.Research progress on pharmacokinetics and residue elimination of antibacterial synergist[J].China Animal Husbandry&Veterinary Medicine,2016,43(12):3141-3148.(in Chinese)
[29] GOMES A R,VARELA C L,PIRES A S,et al.Synthetic and natural guanidine derivatives as antitumor and antimicrobial agents:A review[J].Bioorganic Chemistry,2023,138:106600.
[30] LIU Y,JIA Y,YANG K,et al.Metformin restores tetracyclines susceptibility against multidrug resistant bacteria[J].Advanced Science (Weinh),2020,7(12):1902227.
[31] SAEED A,BOSCH A,BETTIOL M,et al.Novel guanidine compound against multidrug-resistant cystic fibrosis-associated bacterial species[J].Molecules,2018,23(5):1158.
[32] LIU S,LIN L,YANG H,et al. Pasteurella multocida capsular:Lipopolysaccharide types D:L6 and A:L3 remain to be the main epidemic genotypes of pigs in China[J].Animal Diseases,2021,1(1):26.
[33] SHARMA J,SHARMA D,SINGH A,et al.Colistin resistance and management of drug resistant infections[J].Canadian Journal of Infectious Diseases&Medical Microbiology,2022,2022:4315030.
[34] DOMALAON R,DE SILVA P M,KUMAR A,et al.The anthelmintic drug niclosamide synergizes with colistin and reverses colistin resistance in Gram-negative bacilli[J].Antimicrobial Agents and Chemotherapy,2019,63(4):e02574-18.
[35] HUANG Y,WANG Z,LIU Z,et al.Gigantol restores the sensitivity of mcr carrying multidrug-resistant bacteria to colistin[J].Phytomedicine,2023,117:154886.
[36] ZHOU Y,LIU B,CHU X,et al.Commercialized artemisinin derivatives combined with colistin protect against critical Gram-negative bacterial infection[J].Communications Biology,2022,5(1):931.
[37] GUO M,TIAN P,LI Q,et al.Gallium nitrate enhances antimicrobial activity of colistin against Klebsiella pneumoniae by inducing reactive oxygen species accumulation[J].Microbiology Spectrum,2023,11(4):e0033423.
[38] LI J,ZHANG X,HAN N,et al.Mechanism of action of isopropoxy benzene guanidine against multidrug-resistant pathogens[J].Microbiology Spectrum,2022,11(1):e3422.
[39] 李艳芹.黏菌素与加米霉素联用对多杀性巴氏杆菌的药动/药效学及作用机制研究[D].广州:华南农业大学,2020. LI Y Q.Study on pharmacokinetic/pharmacodynamic integration and action mechanism of colistin in combination with gamithromycin against Pasteurella multocida[D].Guangzhou:South China Agricultural University,2020.(in Chinese)

In vitro and in vivo Antibacterial Effect of Isopropoxy Benzene Guanidine Combined with Colistin Against Pasteurella multocida

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