Calcium chelating alizarin and other anthraquinones inhibit biofilm formation and the hemolytic activity of Staphylococcus aureus
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 mg/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 Ca2+ 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 a hemolysin hla gene, biofilm related genes (psma, 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.
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