化脓隐秘杆菌CmlA和FloR外排泵抑制剂的筛选  

Screening of CmlA and FloR Efflux Pump Inhibitors of Trueperella pyogenes

作　　者：李旭领 王述琪 林雨菲 张泽辉[1] 郭玉茹 蔡宜彤 田春莲 王盈予 崔璨璨 刘明春[1] LI Xu-ling;WANG Shu-qi;LIN Yu-fei;ZHANG Ze-hui;GUO Yu-ru;CAI Yi-tong;TAN Chun-lian;WANG Ying-yu;CUI Can-can;LIU Ming-chun(College of Animal Science and Veterinary Medicine,Shenyang Agricultural University,Shenyang,Liaoning 110866,China;China Medical University-The Queen’s University of Belfast Joint Colloge,China Medical University,Shenyang,Liaoning 110122,China)

机构地区：[1]沈阳农业大学动物科学与医学学院,辽宁沈阳110866 [2]中国医科大学中英联合学院,辽宁沈阳110122

出　　处：《动物医学进展》2023年第6期52-58,共7页Progress In Veterinary Medicine

基　　金：国家自然科学基金项目(31572564,31972736)。

摘　　要：为了筛选出效果较好的外排泵抑制剂,对化脓隐秘杆菌进行了耐药基因检测、药敏试验、联合药敏试验和尼罗红外排试验。结果显示,cfr、cmlA、floR、fexA、catI、catB基因的检出率分别为9.8%、39.22%、41.18%、11.76%、13.73%和31.37%,未检出optrA、poxtA、fexB、pexA基因;槲皮素、木犀草素、黄芩苷、川陈皮素、芹菜素等5种黄酮类化合物对化脓隐秘杆菌均具有良好的抗菌效果;其中木犀草素与3种酰胺醇类药物联用后均有相加作用,FICI=1;5种黄酮类化合物均可以抑制CmlA和FloR外排蛋白对尼罗红的外排,其中木犀草素的外排抑制能力最强。耐药消除试验发现,木犀草素可以不同程度的消减化脓隐秘杆菌对酰胺醇类药物的耐药性。结果表明,木犀草素可通过抑制CmlA和FloR的外排作用,逆转化脓隐秘杆菌对酰胺醇类药物的耐药性,为木犀草素作为天然外排泵抑制剂的临床开发利用奠定了基础。To select the more effective efflux pump inhibitors,we performed resistance genes detection,susceptibility tests,joint susceptibility tests,and Nile infrared emission tests on Trueperella pyogenes(T.pyogenes).The results showed that the detection rates of cfr,cmlA,floR,fexA,catI,and catB genes were 9.8%,39.22%,41.18%,11.76%,13.73%and 31.37%,respectively,whereas the optrA,poxtA,fexB,and pexA genes were not identified.The five flavonoids,including quercetin,luteolin,baicalin,nobiletin and apigenin,all exhibited good antibacterial effects against T.pyogenes.In particular,luteolin had an additive effect after combining with three amphenicol antibiotics,with FICI=1.All five flavonoids can inhibit the efflux of CmlA and FloR efflux proteins to Nile red,of which luteolin has the strongest efflux inhibition ability.We found that luteolin can reduce the resistance of T.pyogenes to amphenicol antibiotics to varying degrees by resistance elimination tests.Our data suggest that luteolin may reverse the resistance of T.pyogenes to amphenicol antibiotics by inhibiting the efflux of CmlA and FloR.This study provides the basis for the clinical exploitation of luteolin as a natural efflux pump inhibitor.

关 键 词：化脓隐秘杆菌 黄酮类化合物 外排泵抑制剂 CmlA FloR 

分 类 号：S852.617[农业科学—基础兽医学]