Background:

Daptomycin is a bactericidal antibiotic which works against a broad spectrum of Gram-positive bacteria and it can work both in-vitro and in-vivo. It is a cyclic lipopeptide and many antibiotic resistant strains can be inhibited by daptomycin, such as meticillin-resistant S. aureus (MRSA), vancomycin-intermediate S. aureus (VISA) and vancomycin-resistant S. aureus (VRSA).[1, 2]

The mode of action of Daptomycin would be through a calcium-dependent interaction with the cytoplasmic membrane, thus leading to the cell membrane depolarisation, ion loss and cell death.[2] Daptomycin can bind to the lipid tail of cell membrane of Gram-positive cells, then the following Ca2+ dependent insertion of daptomycin and oligomerization can cause a damage to the bacterial membrane potential, thus kills the cell very fast.[3]

参考文献:
[1] Feng Wang, Ni-Ni Ren, Shuai Luo, Xiao-Xia Chen, Xu-Ming Mao, Yong-Quan Li. DptR2, a DeoR-type auto-regulator, is required for daptomycin production in Streptomyces roseosporus. Gene. 10 July 2014. 544(2): 208-215.
[2] Diixa Patel, Mashkur Husain, Celine Vidaillac, Molly E. Steed, Michael J. Rybak, Susan M. Seo, Glenn W. Kaatz. Mechanisms of in-vitro-selected daptomycin-non-susceptibility in Staphylococcus aureus. International Journal of Antimicrobial Agents. November 2011. 38(5): 442-446.
[3] Yong He, Jing Li, Nin Yin, Prudencio S. Herradura, Larry Martel, Yanzhi Zhang, Andre L. Pearson, Vidya Kulkarni, Carmela Mascio. Reduced pulmonary surfactant interaction of daptomycin analogs via tryptophan replacement with alternative amino acids. Bioorganic & Medicinal Chemistry Letters. 1 October 2012. 22(19): 6248-6251.