title: Dracorhodin Perochlorate attenuates Staphylococcus aureus USA300 virulence by decreasing α-toxin expression.
abstract: α-Toxin, a pore-forming toxin secreted by most Staphylococcus aureus, plays critical role in the pathogenesis associated with various infectious diseases. The USA300 which is a major international epidemic methicilin-resisrant S. aureus has spread rapidly to multiple countries and become an emerging public health concern. In this study, the in vitro efficacy of Dracorhodin Perochlorate (DP) against USA300 virulence was evaluated. Using susceptibility testing, immunoblots, rabbit blood haemolytic assay and real-time RT-PCR, we observed that the α-toxin production was decreased when USA300 was co-cultured with different sub-inhibitory concentration of DP. Further, the protective effect of DP against USA300-mediated injury of human alveolar epithelial cells (A549) and MH-S cells was evaluated by cytotoxicity assays, and the result revealed that DP, at final concentration of 16 µg/ml, is a potent antagonist for USA300-mediated cell damage. Importantly, those beneficial effects might partially correlate with hla and RNAIII suppression by DP, leading to the inhibition of α-toxin production in culture supernatant. Overall, these results suggest that DP could attenuate the virulence of USA300 by decreasing α-toxin production without inhibiting bacterial growth, and this compound may represent an ideal candidate for the development of anti-virulence agent combating S. aureus infection.
authors.affiliation: College of Animal Science and Technology, Jilin Agricultural University, Changchun, 130118, China.|College of Animal Science and Technology, Changchun University of Science and Technology, Changchun, 130600, China.
authors.forename: Yumin
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Key Laboratory of Zoonosis, Ministry of Education, Institute of Zoonosis, College of Veterinary Medicine, Jilin University, Changchun, 130062, China.
authors.forename: Dongxue
authors.initials: D
authors.lastname: Shi
authors.affiliation: Key Laboratory of Zoonosis, Ministry of Education, Institute of Zoonosis, College of Veterinary Medicine, Jilin University, Changchun, 130062, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Guo
authors.affiliation: Key Laboratory of Zoonosis, Ministry of Education, Institute of Zoonosis, College of Veterinary Medicine, Jilin University, Changchun, 130062, China.
authors.forename: Meng
authors.initials: M
authors.lastname: Li
authors.affiliation: Key Laboratory of Zoonosis, Ministry of Education, Institute of Zoonosis, College of Veterinary Medicine, Jilin University, Changchun, 130062, China.
authors.forename: Yonghong
authors.initials: Y
authors.lastname: Zha
authors.affiliation: College of Animal Science and Technology, Jilin Agricultural University, Changchun, 130118, China. 13944125038@163.com.
authors.forename: Quankai
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Key Laboratory of Zoonosis, Ministry of Education, Institute of Zoonosis, College of Veterinary Medicine, Jilin University, Changchun, 130062, China. wjf927@jlu.edu.cn.
authors.forename: Jianfeng
authors.initials: J
authors.lastname: Wang
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001427:Bacterial Toxins / Q000235:genetics* / Q000378:metabolism*; D001578:Benzopyrans / Q000494:pharmacology*; D002460:Cell Line; D002470:Cell Survival; D015536:Down-Regulation; D015964:Gene Expression Regulation, Bacterial / Q000187:drug effects; D006460:Hemolysin Proteins / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects / Q000472:pathogenicity*; D008826:Microbial Sensitivity Tests; D011817:Rabbits; D014774:Virulence / Q000187:drug effects
chemical_list: D000900:Anti-Bacterial Agents; D001427:Bacterial Toxins; D001578:Benzopyrans; D006460:Hemolysin Proteins; C021091:staphylococcal alpha-toxin; C060327:dracorhodin
keywords: Anti-virulence; Dracorhodin Perochlorate; Staphylococcus aureus; USA300; α-Toxin