High-Throughput Drug Screening on Borrelia garinii and Borrelia afzelii Identified Hypocrellin A as an Active Drug Candidate Against Borrelia Species  

作　　者：Tingting Li Yuxian Xin Dongxia Liu Jingrong Sun Jingwei Li Ying Zhang Jie Feng 

机构地区：[1]School of Basic Medical Sciences,Lanzhou University,Lanzhou,China [2]State Key Laboratory for the Diagnosis and Treatment of Infectious Diseases,The First Affiliated Hospital,Zhejiang University School of Medicine,Hangzhou,China [3]Jinan Microecological Biomedicine Shandong Laboratory,Jinan,China [4]State Key Laboratory of Veterinary Etiological Biology,College of Veterinary Medicine,Lanzhou University,Lanzhou,China.

出　　处：《Infectious Microbes & Diseases》2023年第2期83-92,共10页感染微生物与疾病（英文）

基　　金：the National Natural Science Foundation of China(no.81902099);the State Key Laboratory of Veterinary Etiological Biology,Lanzhou Veterinary Research Institute,Chinese Academy of Agricultural Sciences(no.SKLVEB2020KFKT005).

摘　　要：Lyme disease(LD)is a tick-transmitted infection caused by Borrelia burgdorferi sensu lato species,which include B.burgdorferi,Borrelia afzelii and Borrelia garinii.The majority of patients with early LD can be cured by the standard treatment,yet some still suffer from posttreatment LD syndrome.The presence of Borrelia persisters has been proposed as a contributing factor,because they cannot be completely eradicated by the currently used antibiotics for LD.Finding new pharmaceuticals targeting Borrelia persisters is crucial for developing more effective treatments.Here,we first confirmed the existence of persisters in B.garinii and B.afzelii cultures and then conducted a high-throughput screening of a customdrug library against persister-rich stationary-phase B.garinii and B.afzelii cultures.Among 2427 compounds screened,hypocrellin A(HA),anthracycline class of drugs and topical antibiotics along with some other natural compounds were identified to have strong potential for killing persisters of B.garinii and B.afzelii.HA was the most active anti-Borrelia compound,capable of eradicating stationary-phase Borrelia persisters,in particular when combined with doxycycline and/or ceftriaxone.Liposoluble antioxidant vitamin E was found to antagonize the activity of HA,indicating HA’s target is the cell membrane where HA triggers the generation of reactive oxygen species in the presence of light.HA was found to have distinct bactericidal activity against Borrelia species but had poor or no activity against gram-positive and gram-negative bacteria.Identification of the abovementioned drug candidates may help develop more effective therapies for LD.

关 键 词：drug screening Borrelia afzelii Borrelia garinii persister hypocrellin A BIOFILM 

分 类 号：R28[医药卫生—中药学]