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.
Protocol
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Cell experiment [1]:
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Cell lines
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Methicillin susceptible S. aureus (ATCC #29213)
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Preparation method
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The solubility of this compound in DMSO is >81.1mg/mL. General tips for obtaining a higher concentration: Please warm the tube at 37℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months.
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Reacting condition
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MIC: l μg/mL
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Applications
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In methicillin susceptible S. aureus (ATCC #29213), Daptomycin (DAP) maintained good antibacterial activities against S. auerus in Mueller-Hinton Broth supplemented with 50 mg/L calcium (MHBc).
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Animal experiment [2]:
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Animal models
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murine model of enterococcal experimental peritonitis
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Dosage form
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50 mg/kg; q24h, intravenous (i.v.); 2 h after enterococcal inoculation for 48 h
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Application
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In mice injected intraperitoneally with 4 × 1010 colony-forming units of Enterococcus faecium, Daptomycin (DAP) significantly prolonged the mean time until death. DAP or DAP plus AMP significantly decreased the viable bacteria counts of the peritoneal fluid 6 h after inoculation.
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Other notes
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Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal.
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参考文献:
[1] 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.
[2] Kajihara T1, Nakamura S2, Iwanaga N3, et al. Comparative efficacies of daptomycin, vancomycin, and linezolid in experimental enterococcal peritonitis. J Infect Chemother. 2017 Jul;23(7):498-501.
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