Siamycin I is a tricyclic peptide originally isolated from Streptomyces and has antiviral and antibacterial activities. It is active against laboratory strains and clinical isolates of HIV-1 (ED50s = 0.05-0.45 and 0.89-5.7 μM, respectively), as well as the CBL-20 strain of HIV-2 (ED50 = 0.45 μM), in vitro. Siamycin I inhibits HIV-induced fusion of C8166 T cells with HIV-1-infected CEM-SS cells with an ED50 value of 0.08 μM. It is also active against B. subtilis, M. luteus, and S. aureus (MICs = 1.6-6.3 μg/ml). Siamycin I inhibits autophosphorylation of the E. faecalis quorum sensing kinase FsrC induced by gelatinase biosynthesis-activating pheromone (GBAP).