Lipopeptide surfactin ameliorates the cell uptake of platensimycin and enhances its therapeutic effect on treatment of MRSA skin infection.

OBJECTIVES: The rapid development of drug-resistant bacteria, especially MRSA, poses severe threats to global public health. Adoption of antibiotic adjuvants has proved to be one of the efficient ways to solve such a crisis. Platensimycin and surfactin were comprehensively studied to combat prevalent MRSA skin infection. METHODS: MICs of platensimycin, surfactin or their combinations were determined by resazurin assay, while the corresponding MBCs were determined by chequerboard assay. Growth inhibition curves and biofilm inhibition were determined by OD measurements. Membrane permeability analysis was conducted by propidium iodide staining, and morphological characterizations were performed by scanning electron microscopy. Finally, the therapeutic effects on MRSA skin infections were evaluated in scald-model mice. RESULTS: The in vitro assays indicated that surfactin could significantly improve the antibacterial performance of platensimycin against MRSA, especially the bactericidal activity. Subsequent mechanistic studies revealed that surfactin not only interfered with the biofilm formation of MRSA, but also disturbed their cell membranes to enhance membrane permeability, and therefore synergistically ameliorated MRSA cellular uptake of platensimycin. Further in vivo assessment validated the synergistic effect of surfactin on platensimycin and the resultant enhancement of therapeutical efficacy in MRSA skin-infected mice. CONCLUSIONS: The combination of effective and biosafe surfactin and platensimycin could be a promising and efficient treatment for MRSA skin infection, which could provide a feasible solution to combat the major global health threats caused by MRSA.

Surfactin Ameliorated the Internalization and Inhibitory Performances of Bleomycin Family Compounds in Tumor Cells.

The cationic glycopeptide bleomycin (BLM) is a broad-spectrum chemotherapy drug clinically applied to treat various malignant tumors. The poor cell membrane permeability of BLM, which is prone to high dose usage and may consequently induce dose-dependent lung toxicity, is a sticking point to limit clinical applications of BLM. As a commercial biosurfactant, the anionic lipopeptide surfactin (SF) is well known for its potent ability to disturb membranes and widely applied in cosmetic area as a permeabilization synergist. In this work, our in vitro investigations showed that SF could ameliorate the cell internalization of BLM, and the combined usage of SF notably improved the antitumor activity of BLM or its analogues while having no obvious effects on normal cells. Subsequent in vivo assessments on the subcutaneous treatment of A375 melanoma in mice demonstrated that SF could also enhance the therapeutic effects of BLM family compounds in subeffective doses, with no obvious toxicities on lungs and skin. Also, our preliminary results suggested the formation of complex micelles at the nanoscale by the self-assembly of BLM and SF, which may contribute to the ameliorated internalization and the antitumor effect of BLM. Therefore, SF could be applied as a potential synergist for BLM to reduce its treatment dose while maintaining the therapeutic effect on treatment of skin carcinoma, which provides us an alternative way to minimize the side effects of clinical BLM and facilitate the development of new BLM-type drugs.