Wang Hong-hai

Daptomycin: putative new mechanisms of action and resistance evolved from transcriptome data mining.

Daptomycin (Cubicin) is a newly approved effective antibiotic for treatment of the complex skin infections and structure skin infections caused by Gram-positive bacteria, heart infections and bacteremia caused by Staphylococcus aureus which are major scourge of nosocomial-infection and community-infection. However, treatment failures due to lowering of the drug sensitivity are invariantly reported. But the mechanism of action and the contribution factors of decreased sensitivity to daptomycin remain elusive and contentious. In-depth analysis of genome-wide microarray based transcriptome data may facilitate pinpointing the daptomycin targets and regulatory networks pivotal to its efficacy. In this paper, we summarized the structure, mechanism of action of daptomycin and focused on the specific changes in transcriptome of Staphylococcus aureus response to daptomycin to mine potential targets and mechanism of daptomycin resistance. We propose a working model of daptomycin action sharply contrasting with the prevalent notion, that daptomycin exerts its activity by inducing autolysis of Staphylococcus aureus. The detailed genes and related pathways are enumerated. This merits further experiment validation and might benefit future rational use of datomycin and the development of next generation of lipopeptide antibiotics.

Cu(II) effect on the conformation of regenerated silk fibroin in dilute aqueous solution

Much attention has been paid to the natural mechanism of silkworm spinning due to the impressive mechanical properties of the natural fibers. In this work, we studied the effect of Cu(II) ions on the secondary structure of Bombyx mori regenerated silk fibroin (SF) in dilute solution by circular dichroism (CD). The results indicate that a given amount of Cu(II) induces the SF conformational transition from random coil to βsheet, however, further addition of Cu(II) is unfavorable for this conversion. Meanwhile, the conformational changes induced by Cu(II) follow a nucleationdependent aggregation mechanism, which is similar to that found in Prion protein (PrP) denaturation and Aβpeptide aggregations, leading to the neurodegenerative disease. This work would help one understand further the natural spinning process of silkworm. Additionally, it would be significant for the study of the nervous system diseases, because silk fibroin, extracted in large amounts from Bombyx mori silkworm gland, could be a proper model to study PrP denaturation and Aβ-peptide aggregations.