title: Imperatorin inhibits the expression of alpha-hemolysin in Staphylococcus aureus strain BAA-1717 (USA300).
abstract: Both community-associated and hospital-acquired infections with methicillin-resistant Staphylococcus aureus (MRSA) have been increasingly reported around the world in the past 20 years. In 2006, the Centers for Disease Control and Prevention reported that 64 % of MRSA isolates were of the USA300 clonal type in infected patients in USA. The aim of our study was to estimate the in vitro effect of imperatorin on MRSA strain BAA-1717 (USA300). The effects of imperatorin on alpha-hemolysin (Hla) production, when strain BAA-1717 was co-cultured with sub-inhibitory concentrations of imperatorin, were analysed using susceptibility testing, hemolysis assays, western blotting and real-time PCR. Live/Dead analysis and cytotoxicity assays were employed to examine the protective effect of imperatorin against the strain BAA-1717-mediated injury of human alveolar epithelial cells (A549). The results showed that imperatorin has no anti-S. aureus activity at the tested concentrations in vitro. However, imperatorin can observably inhibit the production of Hla in culture supernatants and reduce the transcriptional levels of hla (the gene encoding Hla) and arg (the accessory gene regulator). Imperatorin prevented Hla-mediated A549 epithelial cell injury in a co-culture system. In conclusion, our results suggested that imperatorin has the potential to be developed as a new anti-virulence drug candidate for managing S. aureus infection.
authors.affiliation: College of Veterinary Medicine, Sichuan Agriculture University, Chengdu, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Ouyang
authors.affiliation: College of Veterinary Medicine, Sichuan Agriculture University, Chengdu, China.
authors.forename: Junjie
authors.initials: J
authors.lastname: Chen
authors.affiliation: College of Veterinary Medicine, Sichuan Agriculture University, Chengdu, China.
authors.forename: Mao
authors.initials: M
authors.lastname: Sun
authors.affiliation: College of Veterinary Medicine, Sichuan Agriculture University, Chengdu, China.
authors.forename: Zhongqiong
authors.initials: Z
authors.lastname: Yin
authors.affiliation: College of Veterinary Medicine, Sichuan Agriculture University, Chengdu, China.
authors.forename: Juchun
authors.initials: J
authors.lastname: Lin
authors.affiliation: College of Veterinary Medicine, Sichuan Agriculture University, Chengdu, China.
authors.forename: Hualin
authors.initials: H
authors.lastname: Fu
authors.affiliation: College of Veterinary Medicine, Sichuan Agriculture University, Chengdu, China.
authors.forename: Gang
authors.initials: G
authors.lastname: Shu
authors.affiliation: College of Veterinary Medicine, Sichuan Agriculture University, Chengdu, China.
authors.forename: Changliang
authors.initials: C
authors.lastname: He
authors.affiliation: College of Veterinary Medicine, Sichuan Agriculture University, Chengdu, China.
authors.forename: Cheng
authors.initials: C
authors.lastname: Lv
authors.affiliation: College of Veterinary Medicine, Jilin University, Changchun, China.
authors.forename: Xuming
authors.initials: X
authors.lastname: Deng
authors.affiliation: College of Veterinary Medicine, Sichuan Agriculture University, Chengdu, China.
authors.forename: Kaiyu
authors.initials: K
authors.lastname: Wang
authors.affiliation: College of Veterinary Medicine, Sichuan Agriculture University, Chengdu, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Geng
authors.affiliation: College of Veterinary Medicine, Sichuan Agriculture University, Chengdu, China. yinlizi@sicau.edu.cn.
authors.forename: Lizi
authors.initials: L
authors.lastname: Yin
mesh_terms: D000072283:A549 Cells; D056809:Alveolar Epithelial Cells / Q000382:microbiology; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001427:Bacterial Toxins / Q000096:biosynthesis* / Q000235:genetics; D018920:Coculture Techniques; D011564:Furocoumarins / Q000494:pharmacology*; D006460:Hemolysin Proteins / Q000096:biosynthesis* / Q000235:genetics; D006461:Hemolysis; D006801:Humans; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects* / Q000378:metabolism; D008826:Microbial Sensitivity Tests
chemical_list: D000900:Anti-Bacterial Agents; D001427:Bacterial Toxins; D011564:Furocoumarins; D006460:Hemolysin Proteins; C021091:staphylococcal alpha-toxin; C031534:imperatorin
keywords: Alpha-hemolysin; Imperatorin; Methicillin-resistant Staphylococcus aureus; USA300; Virulence factor