Search Method for Inhibitors of Staphyloxanthin Production by Methicillin-Resistant Staphylococcus aureus

Abstract

Staphyloxanthin, a yellow pigment produced by methicillin-resistant Staphylococcus aureus (MRSA), is a virulent factor escaping from the host immune system. A new screening method for inhibitors of staphyloxanthin production by MRSA was established using paper disks. By this screening method, inhibitors of staphyloxanthin production were selected from the natural product library (ca. 300) and from actinomycete culture broths (ca. 1000). From the natural product library, four known inhibitors of lipid metabolism, cerulenin, dihydrobisvertinol, xanthohumol and zaragozic acid, were found to inhibit staphyloxanthin production; however, typical antibiotics used clinically, including vancomycin, had no effect on staphyloxanthin production. From actinomycete culture broths, two known anthraquinones, 6-deoxy-8-O-methylrabelomycin and tetrangomycin, were found to inhibit staphyloxanthin production by MRSA in the paper disk assay. These results suggested that this screening method is useful and effective to find compounds targeting staphyloxanthin production, leading to a new type of chemotherapeutics against MRSA infection.

Angucyclines and Angucyclinones from Streptomyces sp. CB01913 Featuring C-Ring Cleavage and Expansion

“…As summarized in Table 5, both 15 and 16 showed moderate activity against S. aureus ATCC 25923, B. subtilis ATCC 23857, and M. smegmatis ATCC 607, with the minimum inhibitory concentration (MIC) values ranging from 8.1 to 25 µg/mL, which were similar to the reported MIC values for 15 and 16 against other S. aureus or B. subtilis species. 26, 27, 32–34 Compound 5 showed weak activity against B. subtilis ATCC 23857 and M. smegmatis ATCC 607. As previously observed for known angucyclines and angucyclinones, 2 1–16 showed no activity against the Gram-negative E. coli ATCC 25922 and JM109 species.…”

Antiadherent and Antibiofilm Activity ofHumulus lupulusL. Derived Products: New Pharmacological Properties

“…This demonstrates the importance of structure of cell wall/membrane and its permeability rather than metabolic activity of these microorganisms. It is not without significance the fact that, as was described by Sakai et al [20], xanthohumol (an inhibitor of diacylglycerol acyltransferase) and natural products which contain this compound (hop extract) belong to the group of products which are potent inhibitors of lipid metabolism. This can significantly affect the composition and stability of microbial cell wall/membrane.…”

Targeting virulence factors as an antimicrobial approach: Pigment inhibitors

“…By determining the structure of ZA‐A complexed with either human SQS or CrtM, Wang and Liu elucidated how the 2,8‐dioxabicyclo[3.2.1]octane‐3,4,5‐tricarboxylic acid core fine‐tunes the selective effects against these two enzymes. In recent years, Hiroshi Tomoda's group has exhibited meaningful work on the discovery of STX inhibitors by creating a microbial metabolite library . They placed microbial culture sample‐containing paper disks on an MRSA agar plate and investigated whether the color of zone‐showing samples transferred to white or not (meaning that the yellow STX pigment production was inhibited, while MRSA grew normally).…”