Bacterial lipopeptides

Surfactin Bacterial lipopeptide biosurfactant inhibits clot formation (387)... 

Bessler WG, et al. Bacterial lipopeptides constitute efficient novel immunogens and adjuvants in parenteral and oral immunization. Behring Inst Mitt 1997 98 390. 

Schromm, A.B., Howe, J., Ulmer, A.J., Wiesmuller, K.H., Seyberth, T., Jung, G., Rossle, M., Koch, M.H., Gutsmann, T., Brandenburg, K. Physicochemical and biological analysis of synthetic bacterial lipopeptides validity of the concept of endotoxic conformation. J Biol Chem 282 (2007) 11030-11037. 

Morr, M., Takeuchi, O., Akashi, S., Simon, M.M., Muhlradt, P.F. Differential recognition of structural details of bacterial lipopeptides by Toll-like receptors. Eur J Immunol 32 (2002)... 

Marion, D., M. Genest, A. Caille, F. Peypoux, G. Michel, and M. Ptak Conformational Study of Bacterial Lipopeptides Refinement of the Structure of iturin A in Solution by Two Dimensional H-NMR and Energy Calculations. Biopolymers 25, 153 (1986). 

Maget-Dana, R., F. Heitz, M. Ptak, F. Peypoux, and M. Guinand Bacterial Lipopeptides Induce Ion-Conducting Pores in Planar Bilayers. Biochem. Biophys. Res. Comm. 129, 965 (1985). 

New insights into the analysis of hydrophobically post-translational modified proteins could be achieved by the construction of lipidated proteins in a combination of bioorganic synthesis of activated lipopeptides and bacterial expression of the protein backbone (Fig. 19). The physico-chemical properties of such artificial lipoproteins differ substantially from those of the corresponding lipopeptides. The pronounced dominance of the hydrophilic protein moiety (e.g., for the Ras protein 181 amino acids) over a short lipopeptide with one or two hydrophobic modifications provides solubility up to 10 4 mol/1, while the biotinylated or fluorescence labeled lipopeptides exhibit low solubility in aqueous solutions and can be applied in the biophysical experiments only in vesicle integrated form or dissolved in organic solvent. 

Daptomycin (15 Cubicin ) Daptomycin (15) Lipopeptide NP Microbial Antibacterial Disrupts multiple aspects of bacterial cell membrane function 211-225... 

Ramoplanin (142) Lipopeptide Ramoplanin factor Antibacterial Inhibits bacterial cell Phase II Oscient 772-777... 

A novel cyclic lipopeptide antibiotic was isolated from cultures of Strep-tomyces roseosporus grown in the presence of decanioc acid. Daptomycin interacts with the bacterial cell membrane and interferes with membrane potential.Unlike polymyxin B, daptomycin can target majority of clinically relevant Gram-positive pathogens. 

Mechanism of Action A lipopeptide antibacterial agent that binds to bacterial membranes and causes a rapid depolarization of the membrane potential. The loss of membrane potential leads to inhibition of protein, DNA, and RNA synthesis. Therapeutic Effect Bactericidal. 

Takahashi, T., Ohno, O., Ikeda, Y., Sawa, R., Homma, Y., Igarashi, M., and Umezawa, K. (2006). Inhibition of lipopolysaccharide activity by a bacterial cyclic lipopeptide surfactin. ]. Antibiot. 59, 35-43. 

Mineral Salts Immunostimulatory adjuvants Lipid particles Particulate adjuvants Mucosal adjuvants Aluminium hydroxide, aluminium phosphate, calcium phosphate Saponins (e.g., QS21), MDP derivatives, bacterial DNA (CpG oligos), LPS, MPL and synthetic derivatives, lipopeptides, cytokines (e.g., GM-CSF, IL-2, IL-12) Liposomes, virosomes, iscoms, cochleates, emulsions (e.g., Freunds adjuvant, SAF, MF59 ) Poloxamer particles, virus-like particles, PLG microparticles Cholera toxin (CT), mutant toxin (e.g., LTK63, LTR72), heat labile enterotoxin (LT), microparticles, polymerized liposomes, chitosan... 

Chemical characterization hypothesizes that certain molecules are unique and representative of individual microorganisms, and therefore the mass spectra can be characteristic of given species. A typical bacterial spectrum obtained by MALDI-TOF usually contains between 20 and 40 large peaks, mainly produced by proteins, phospholipids, and cyclic lipopeptides, in the MW range of 4—20 kDa.31 ESI is less frequently used samples containing intact cells can clog electrospray devices, and the formation of multiply charged species complicates the spectra. 

Daptomycin was originally isolated from the soil saprotroph Streptomyces roseos-porus by scientists at Eli Lilly and Company in the 1980s. It is a novel lipopeptide antibiotic used in the treatment of certain infections caused by Gram-positive organisms. The proposed mechanism of action involves insertion of the lipophilic daptomycin tail into the bacterial cell membrane, causing rapid membrane depolarization and a potassium ion efflux. This leads to the arrest of DNA, RNA, and protein synthesis, resulting in bacterial cell death (see footnote 1). 

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