title: Calcium-chelating alizarin and other anthraquinones inhibit biofilm formation and the hemolytic activity of Staphylococcus aureus.
abstract: Staphylococcal biofilms are problematic and play a critical role in the persistence of chronic infections because of their abilities to tolerate antimicrobial agents. Thus, the inhibitions of biofilm formation and/or toxin production are viewed as alternative means of controlling Staphylococcus aureus infections. Here, the antibiofilm activities of 560 purified phytochemicals were examined. Alizarin at 10 μg/ml was found to efficiently inhibit biofilm formation by three S. aureus strains and a Staphylococcus epidermidis strain. In addition, two other anthraquinones purpurin and quinalizarin were found to have antibiofilm activity. Binding of Ca(2+) by alizarin decreased S. aureus biofilm formation and a calcium-specific chelating agent suppressed the effect of calcium. These three anthraquinones also markedly inhibited the hemolytic activity of S. aureus, and in-line with their antibiofilm activities, increased cell aggregation. A chemical structure-activity relationship study revealed that two hydroxyl units at the C-1 and C-2 positions of anthraquinone play important roles in antibiofilm and anti-hemolytic activities. Transcriptional analyses showed that alizarin repressed the α-hemolysin hla gene, biofilm-related genes (psmα, rbf, and spa), and modulated the expressions of cid/lrg genes (the holin/antiholin system). These findings suggest anthraquinones, especially alizarin, are potentially useful for controlling biofilm formation and the virulence of S. aureus.
authors.affiliation: School of Chemical Engineering, Yeungnam University, Gyeongsan, 712-749, Republic of Korea.
authors.forename: Jin-Hyung
authors.initials: JH
authors.lastname: Lee
authors.affiliation: School of Chemical Engineering, Yeungnam University, Gyeongsan, 712-749, Republic of Korea.
authors.forename: Yong-Guy
authors.initials: YG
authors.lastname: Kim
authors.affiliation: Korea Research Institute of Chemical Technology, Daejeon, 305-606, Republic of Korea.
authors.forename: Shi
authors.initials: S
authors.lastname: Yong Ryu
authors.affiliation: School of Chemical Engineering, Yeungnam University, Gyeongsan, 712-749, Republic of Korea.
authors.forename: Jintae
authors.initials: J
authors.lastname: Lee
mesh_terms: D000814:Aniline Compounds / Q000494:pharmacology*; D000880:Anthraquinones / Q000494:pharmacology*; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D018441:Biofilms / Q000187:drug effects*; D020869:Gene Expression Profiling; D015964:Gene Expression Regulation, Bacterial / Q000187:drug effects; D006461:Hemolysis / Q000187:drug effects*; D008826:Microbial Sensitivity Tests; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000502:physiology*; D013212:Staphylococcus epidermidis / Q000187:drug effects / Q000502:physiology; D059467:Transcriptome
chemical_list: D000814:Aniline Compounds; D000880:Anthraquinones; D000900:Anti-Bacterial Agents; C004354:dicloran