HIV is a virus that affects the immune system. HIV infects important cells in the human immune system, such as helper T cells (especially CD4+T cells), macrophages, and dendritic cells. Meanwhile, HIV infection leads to a low level of CD4+T cells through a variety of mechanisms, including the charred death of T cells infected by abortion, and the apoptosis of uninfected bystanders. Nonetheless, Lipid II is a membrane-anchored cell wall precursor, which is essential for bacterial cell wall biosynthesis. Besides, the effectiveness of targeted lipid II as an antibacterial strategy is highlighted in that it is the target of at least four different types of antibiotics. Almost all bacteria contain peptidoglycan cell walls.

The peptidoglycan precursor molecule is Lipid II, which contains the basic peptidoglycan structural unit connected with lipids. The biosynthesis of peptidoglycan occurs in the cytoplasm, while the key precursor lipid II is synthesized on the cell membrane. Moreover, Many antibiotics target cell wall biosynthesis. Here, we will introduce an HIV Fusion Inhibitor which interacts with lipid II and inhibits cell wall biosynthesis, Siamycin I.

Siamycin I, an HIV Fusion Inhibitor, Interacts with Lipid II and Inhibits Cell Wall Biosynthesis.

Above all, Siamycin I (BMY-29304), a 21-residue tricyclic peptide, is a secondary metabolite in actinomycetes. Furthermore, Siamycin I is an HIV fusion inhibitor with ED_50s of 0.05 to 5.7 μM for acute HIV-1 and HIV-2 infections. Specifically, Siamycin I inhibits the gelatinous and gelatinous biosynthesis-activating pheromone (GBAP) signaling via the FsrC-FsrA two-component regulatory system in a non-competitive manner. Importantly, Siamycin I suppresses the expression of both fsrBDC and gelE-sprE transcripts. Siamycin I, a lasso peptide, interacts with lipid II and inhibits cell wall biosynthesis. Siamycin I, an antibiotic, has the potential for enterococcal infections research.

Next in importance, Siamycin I slightly inhibits the growth of E. faecalis at a concentration of 1 μM (80% growth 5 h after inoculation). Siamycin I completely inhibits the growth at a concentration of 5 μM (no growth 12 h after inoculation). Particularly, Siamycin I slightly inhibits biofilm formation at a concentration of 0.25 μM. Obviously, the inhibitory effect is marked at concentrations higher than 0.5 μM.
Once again, Siamycin I inhibits fusion between C8166 cells and CEM-SS cells chronically infected with HIV (ED₅₀=0.08 μM). In fact, Siamycin I has no effect on Sendai virus-induced fusion or murine myoblast fusion.

All in all, Siamycin I, an HIV fusion inhibitor, interacts with lipid II and inhibits cell wall biosynthesis.

References:

[1]  Jiro Nakayama, et al. J Bacteriol. 2007 Feb;189(4):1358-65.

[1]  M Tsunakawa, et al. J Antibiot (Tokyo). 1995 May;48(5):433-4.