antivirulence

MAC-545496 is a glycopeptide-resistance-associated protein R (GraR) inhibitor, is an antivirulence agent.

Anti-virulence factor-IN-2 (compound C7) is an inhibitor targeting the virulence factor KpsM in Escherichia coli. KpsM facilitates the translocation of capsular polysaccharides to the cell surface, enabling KpsM-positive E. coli to evade phagocytosis by the scavenger receptor Marco on liver Kupffer cells, promoting bacterial dissemination. These bacteria can exacerbate ethanol-induced liver disease. Anti-virulence factor-IN-2 demonstrates anti-infective activity by inhibiting KpsM-dependent capsulation in a mouse model of ethanol-induced liver disease. This compound is applicable for alcoholic hepatitis research.

Anti-virulence factor-IN-3 (Compound 21) is a covalent β-amino sulfone inhibitor of anthrax edema factor (EF), with a Ki of 0.44 μM. It produces an active vinyl sulfone intermediate that forms an irreversible covalent bond with the Lys residue at the EF active site, permanently inhibiting the adenylate cyclase activity of EF. Anti-virulence factor-IN-3 effectively suppresses EF-induced cAMP production, with an EC50 of 0.15 μM, and can be used in the study of anthrax infection.

UM-C162, a benzimidazole derivative, offers protection to nematodes from Staphylococcus aureus infections. It inhibits biofilm formation without impairing bacterial viability. Additionally, UM-C162 disrupts the production of Staphylococcus aureus hemolysins, proteases, and coagulases. This compound holds potential as an antivirulence agent for managing Staphylococcus aureus infections.

L-NBDNJ is a sugar mimic and an antivirulence agent. It disrupts the expression of proteins that regulate the assembly and organization of the host cell cytoskeleton. In cystic fibrosis (CF) lung disease infection models, L-NBDNJ exhibits both anti-inflammatory and anti-infective properties.

Apicidin D2 (Compound 4) is a fungal metabolite that functions as an AgrA quorum sensing inhibitor. It exhibits antivirulence activity by non-bactericidally inhibiting the activation of methicillin-resistant Staphylococcus aureus (MRSA) Agr, demonstrating potent inhibitory effects on all Agr types. Apicidin D2 is useful for researching MRSA infections.

Obacunone has cytotoxicity in androgen-dependent human prostate Y cells. Obacunone exerts an antivirulence effect on S. Typhimurium and may serve as a lead compound for development of antivirulence strategies for S. Typhimurium. Obacunone may have the pot

Quorum sensing is a regulatory process used by bacteria for controlling gene expression in response to increasing cell density.[1] This regulatory process manifests itself with a variety of phenotypes including biofilm formation and virulence factor production.[2] Coordinated gene expression is achieved by the production, release, and detection of small diffusible signal molecules called autoinducers. The N-acylated homoserine lactones (AHLs) comprise one such class of autoinducers, each of which generally consists of a fatty acid coupled with homoserine lactone (HSL). AHLs vary in acyl group length (C4-C18), in the substitution of C3 (hydrogen, hydroxyl, or oxo group) and in the presence or absence of one or more carbon-carbon double bonds in the fatty acid chain. These differences confer signal specificity through the affinity of transcriptional regulators of the LuxR family.[3] C16:1-Δ9-(L)-HSL is a long-chain AHL that functions as a quorum sensing signaling molecule in strains of S. meliloti.[4],[5],[6],[7] Regulating bacterial quorum sensing signaling can be used to inhibit pathogenesis and thus, represents a new approach to antimicrobial therapy in the treatment of infectious diseases.[8] Reference：[1]. González, J.E., and Keshavan, N.D. Messing with bacterial quorum sensing. Microbiol. Mol. Biol. Rev. 70(4), 859-875 (2006).[2]. Gould, T.A., Herman, J., Krank, J., et al. Specificity of acyl-homoserine lactone syntheses examined by mass spectrometry. J. Bacteriol. 188(2), 773-783 (2006).[3]. Penalver, C.G.N., Morin, D., Cantet, F., et al. Methylobacterium extorquens AM1 produces a novel type of acyl-homoserine lactone with a double unsaturated side chain under methylotrophic growth conditions. FEBS Lett. 580(2), 561-567 (2006).[4]. Teplitski, M., Eberhard, A., Gronquist, M.R., et al. Chemical identification of N-acyl homoserine lactone quorum-sensing signals produced by Sinorhizobium meliloti strains in defined medium. Archives of Microbiology 180, 494-497 (2003).[5]. Gao, M., Chen, H., Eberhard, A., et al. sinI- and expR-dependent quorum sensing in Sinorhizobium meliloti. Journal of Bacteriology 187(23), 7931-7944 (2005).[6]. Marketon, M.M., Glenn, S.A., Eberhard, A., et al. Quorum sensing controls exopolysaccharide production in Sinorhizobium meliloti. Journal of Bacteriology 185(1), 325-331 (2003).[7]. Marketon, M., Gronquist, M.R., Eberhard, A., et al. Characterization of the Sinorhizobium meliloti sinR/sinI locus and the production of novel N-Acyl homoserine lactones. Journal of Bacteriology 184(20), 5686-5695 (2002).[8]. Cegelski, L., Marshall, G.R., Eldridge, G.R., et al. The biology and future prospects of antivirulence therapies. Nat. Rev. Microbiol. 6(1), 17-27 (2008).

Quorum sensing is a regulatory system used by bacteria for controlling gene expression in response to increasing cell density.[1] This regulatory process manifests itself with a variety of phenotypes including biofilm formation and virulence factor production.[2] Coordinated gene expression is achieved by the production, release, and detection of small diffusible signal molecules called autoinducers. The N-acylated homoserine lactones (AHLs) comprise one such class of autoinducers, each of which generally consists of a fatty acid coupled with homoserine lactone (HSL). Regulation of bacterial quorum sensing signaling systems to inhibit pathogenesis represents a new approach to antimicrobial therapy in the treatment of infectious diseases.[3] AHLs vary in acyl group length (C4-C18), in the substitution of C3 (hydrogen, hydroxyl, or oxo group), and in the presence or absence of one or more carbon-carbon double bonds in the fatty acid chain. These differences confer signal specificity through the affinity of transcriptional regulators of the LuxR family.[4] C16-HSL is one of a number of lipophilic, long acyl side-chain bearing AHLs, including its monounsaturated analog C16:1-(L)-HSL, produced by the LuxI AHL synthase homolog SinI involved in quorum-sensing signaling in S. meliloti, a nitrogen-fixing bacterial symbiont of certain legumes.[5],[6] C16-HSL is the most abundant AHL produced by the proteobacterium R. capsulatus and activates genetic exchange between R. capsulatus cells.[7] N-Hexadecanoyl-L-homoserine lactone and other hydrophobic AHLs tend to localize in relatively lipophilic cellular environments of bacteria and cannot diffuse freely through the cell membrane. The long-chain N-acylhomoserine lactones may be exported from cells by efflux pumps or may be transported between communicating cells by way of extracellular outer membrane vesicles.[8],[9]Reference:[1]. González, J.E., and Keshavan, N.D. Messing with bacterial quorum sensing Microbiol. Mol. Biol. Rev. 70(4), 859-875 (2006).[2]. Gould, T.A., Herman, J., Krank, J., et al. Specificity of acyl-homoserine lactone syntheses examined by mass spectrometry Journal of Bacteriology 188(2), 773-783 (2006).[3]. Cegelski, L., Marshall, G.R., Eldridge, G.R., et al. The biology and future prospects of antivirulence therapies Nature Reviews.Microbiology 6(1), 17-27 (2008).[4]. Penalver, C.G.N., Morin, D., Cantet, F., et al. Methylobacterium extorquens AM1 produces a novel type of acyl-homoserine lactone with a double unsaturated side chain under methylotrophic growth conditions FEBS Letters 580, 561-567 (2006).[5]. Gao, M., Chen, H., Eberhard, A., et al. sinI- and expR-dependent quorum sensing in Sinorhizobium meliloti Journal of Bacteriology 187(23), 7931-7944 (2005).[6]. Teplitski, M., Eberhard, A., Gronquist, M.R., et al. Chemical identification of N-acyl homoserine lactone quorum-sensing signals produced by Sinorhizobium meliloti strains in defined medium Archives of Microbiology 180, 494-497 (2003).[7]. Schaefer, A.L., Taylor, T.A., Beatty, J.T., et al. Long-chain acyl-homoserine lactone quorum-sensing regulation of Rhodobacter capsulatus gene transfer agent production Journal of Bacteriology 184(23), 6515-6521 (2002).[8]. Pearson, J.P., Van Delden, C., and Iglewski, B.H. Active efflux and diffusion are involved in transport of Pseudomonas aeruginosa cell-to-cell signals Journal of Bacteriology 181(4), 1203-1210 (1999).[9]. Mashburn-Warren, L., and Whiteley, M. Special delivery: Vesicle trafficking in prokaryotes Molecular Microbiology 61(4), 839-846 (2006).

Quoromycin is a novel antivirulence agent against Vibrio vulnificus, inhibiting the quorum-sensing signaling pathway by controlling the DNA-binding affinity of SmcR and thus effectively alleviating the virulence of V. vulnificus in vitro and in vivo.

SAV13, an analogue of HR3744, is an inhibitor of SaeR that inhibits SaeR-DNA probe binding and possesses antivirulence properties [1].

Obacunone (Standard) is a reference standard for research and analysis in studies involving Obacunone. Obacunone has cytotoxicity in androgen-dependent human prostate Y cells. Obacunone exerts an antivirulence effect on S. Typhimurium and may serve as a lead compound for development of antivirulence strategies for S. Typhimurium. Obacunone may have the potential to prevent estrogen-responsive breast Y through inhibition of the aromatase enzyme and inflammatory pathways, as well as activation of apoptosis.