Physcion, a novel anthraquinone derivative against Chlamydia psittaci infection

Abstract

Physcion, a natural anthraquinone derivative, has been reported to exert remarkable antibacterial activities against Staphylococcus aureus,Staphylococcus epidermidis and Pseudomonas aeruginosa. However, it is not fully illustrated as anti-Chlamydia substance. In the present study, minimum inhibitory concentration(MIC)values for physcion against Chlamydia psittaci(C.psittaci) 6BC, C.psittaci SBL and C.psittaci HJ were 128 μg/mL,256 μg/mL and 128 μg/mL while minimum bactericidal concentration (MBC) values were 256 μg/mL,512 μg/mL and 256 μg/mL,respectively. Moreover, Chlamydial adhesion to Hela 229 cells was blocked in a dose-dependent manner and RB-to-EB differentiation was inhibited by physcion from 28 to 48 hpi.Post treatment,upregulation of LC3-II was in a dose-dependent manner, indicating physcion activated autophagy and bacterial clearance.To validate clinical efficacy,49 SPF chickens aged 21days were divided into 5 groups and infected intra-laryngeally with 0.2 mL of 1 × 10⁷ IFU/mL C.psittaci 6 BCE.Three days later, birds received orally with serial doses of physcion (4 mg/kg to 9 mg/kg), or 3 mg/kg of doxycycline for 6 days.Chickens with difficulty in breathing were alleviated significantly with increasing concentrations of physicon.Postmortem,lesions of air sacs were reduced significantly in a dose-dependent manner.More importantly,birds with 9 mg/kg of physcion could alleviate lesions of air sacs and lungs, and reduce bacterial loads in spleens, which was comparable to doxycycline treatment. Based on above evidences, physcion is a promising cost-effective natural drug by blocking Chlamydial adhesions to host cells, RB-to-EB differentiation and activating bacterial autophagy and it will be a good alternative to doxycycline combating virulent C.psittaci infection, contributing to eradication of Chlamydial transmission from animals to human beings.

Keywords: Autophagy; Chlamydia psittaci; Efficacy; Elementary body; Physcion; Reticular body.