Isovitexin Is a Direct Inhibitor of Staphylococcus aureus Coagulase
4
조회
0
다운로드
1
인용
0
참고문헌
키워드
초록
Staphylococcus aureus (S. aureus) is a major pathogen that causes human pneumonia, leading to significant morbidity and mortality. S. aureus coagulase (Coa) triggers the polymerization of fibrin by activating host prothrombin, which then converts fibrinogen to fibrin and contributes to S. aureus pathogenesis and persistent infection. In our research, we demonstrate that isovitexin, an active traditional Chinese medicine component, can inhibit the coagulase activity of Coa but does not interfere with the growth of S. aureus. Furthermore, we show through thermal shift and fluorescence quenching assays that isovitexin directly binds to Coa. Dynamic simulation and structure-activity relationship analyses suggest that V191 and P268 are key amino acid residues responsible for the binding of isovitexin to Coa. Taken together, these data indicate that isovitexin is a direct Coa inhibitor and a promising candidate for drug development against S. aureus infection.
Abstract
Staphylococcus aureus (S. aureus) is a major pathogen that causes human pneumonia, leading to significant morbidity and mortality. S. aureus coagulase (Coa) triggers the polymerization of fibrin by activating host prothrombin, which then converts fibrinogen to fibrin and contributes to S. aureus pathogenesis and persistent infection. In our research, we demonstrate that isovitexin, an active traditional Chinese medicine component, can inhibit the coagulase activity of Coa but does not interfere with the growth of S. aureus. Furthermore, we show through thermal shift and fluorescence quenching assays that isovitexin directly binds to Coa. Dynamic simulation and structure-activity relationship analyses suggest that V191 and P268 are key amino acid residues responsible for the binding of isovitexin to Coa. Taken together, these data indicate that isovitexin is a direct Coa inhibitor and a promising candidate for drug development against S. aureus infection.
참고문헌 (40)
- Tong SY, "Staphylococcus aureus infections : epidemiology, pathophysiology, clinical manifestations, and management", Clin. Microbiol. Rev, 28, pp.603~661 (2015)
- Turner NA, "Methicillin-resistant Staphylococcus aureus : an overview of basic and clinical research", Nat. Rev. Microbiol, 17, pp.203~218 (2019)
- Assis LM, "New strategies for targeting and treatment of multi-drug resistant Staphylococcus aureus", Drug Resist. Updat, 31, pp.1~14 (2017)
- Thammavongsa V, "Staphylococcal manipulation of host immune responses", Nat. Rev. Microbiol, 13, pp.529~543 (2015)
- Mühlen S, "Anti-virulence strategies to target bacterial infections", Curr. Top. Microbiol. Immunol, 398, pp.147~183 (2016)
- Loeb L, "The influence of certain bacteria on the coagulation of the blood", J. Med. Res, 10, pp.407~419 (1903)
- Bjerketorp J, "The von Willebrand factor-binding protein(vWbp)of Staphylococcus aureus is a coagulase", FEMS Microbiol. Lett, 234, pp.309~314 (2004)
- Kroh HK, "Von Willebrand factor-binding protein is a hysteretic conformational activator of prothrombin", Proc. Natl. Acad. Sci. USA, 106, pp.7786~7791 (2009)
- Friedrich R, "Staphylocoagulase is a prototype for the mechanism of cofactor-induced zymogen activation", Nature, 425, pp.535~539 (2003)
- Ichinose A, "Factor XIII is a key molecule at the intersection of coagulation and fibrinolysis as well as inflammation and infection control", Int. J. Hematol, 95, pp.362~370 (2012)
- Foster TJ, "The MSCRAMM family of cell-wall-anchored surface proteins of Gram-positive cocci", Trends Microbiol, 27, pp.927~941 (2019)
- McAdow M, "Preventing Staphylococcus aureus sepsis through the inhibition of its agglutination in blood", PLoS Pathog, 7, pp.e1002307~ (2011)
- Sawai T, "Role of coagulase in a murine model of hematogenous pulmonary infection induced by intravenous injection of Staphylococcus aureus enmeshed in agar beads", Infect. Immun, 65, pp.466~471 (1997)
- Cheng AG, "Contribution of coagulases towards Staphylococcus aureus disease and protective immunity", PLoS Pathog, 6, pp.e1001036~ (2010)
- Vanassche T, "Fibrin formation by staphylothrombin facilitates Staphylococcus aureus-induced platelet aggregation", Thromb. Haemost, 107, pp.1107~1121 (2012)
- Bock PE, "Exosites in the substrate specificity of blood coagulation reactions", J. Thromb. Haemost., 5(Suppl 1), pp.81~94 (2007)
- Peetermans M, "Coagulase activity by Staphylococcus aureus: a potential target for therapy?", Semin. Thromb. Hemost, 41, pp.433~444 (2015)
- Vanassche T, "Dabigatran inhibits Staphylococcus aureus coagulase activity", J. Clin. Microbiol, 48, pp.4248~4250 (2010)
- Alatri A, "Results of a consensus meeting on the use of argatroban in patients with heparin-induced thrombocytopenia requiring antithrombotic therapy-a European Perspective", Thromb. Res, 129, pp.426~433 (2012)
- Lillo-Le Louët A, "Life-threatening bleeding in four patients with an unusual excessive response to dabigatran : implications for emergency surgery and resuscitation", Thromb. Haemost, 108, pp.583~585 (2012)
- Zhang H, "Uncariitannin, a polyphenolic polymer from Uncaria gambier, attenuates Staphylococcus aureus virulence through an MgrA-mediated regulation of α-hemolysin", Pharmacol. Res, 147, pp.104328~ (2019)
- Duan J, "Subinhibitory concentrations of resveratrol reduce alpha-hemolysin production in Staphylococcus aureus isolates by downregulating saeRS", Emerg. Microbes Infect, 7, pp.136~ (2018)
- Wang L, "Quercetin protects rats from catheter-related Staphylococcus aureus infections by inhibiting coagulase activity", J. Cell. Mol. Med, 23, pp.4808~4818 (2019)
- He M, "A review on the pharmacological effects of vitexin and isovitexin", Fitoterapia, 115, pp.74~85 (2016)
- Xiao Z, "Clostridium Tyrobutyricum protect intestinal barrier function from LPSinduced apoptosis via P38", JNK signaling pathway in IPEC-J2 cells, 2018, pp.46, 1779~1792
- Hwang SM, "Improved methods for detection and serotyping of coagulase from Staphylococcus aureus", Microbiol. Immunol, 33, pp.175~182 (2013)
- Krishna SN, "A fluorescence-based thermal shift assay identifies inhibitors of mitogen activated protein kinase kinase 4", PLoS One, 8, pp.e81504~ (2013)
- Bell L, "Evaluation of fluorescence-and mass spectrometry-based CYP inhibition assays for use in drug discovery", J. Biomol. Screen, 13, pp.343~353 (2008)
- Sok V, "Kinetic, spectroscopic and computational docking study of the inhibitory effect of the pesticides 2, 4, 5-T, 2, 4-D and glyphosate on the diphenolase activity of mushroom tyrosinase", Int. J. Biol. Macromol, 118, pp.427~434 (2018)
- Sanner MF, "Python : a programming language for software integration and development", J. Mol. Graph. Model, 17, pp.57~61 (1999)
- Morris GM, "AutoDock4 and AutoDockTools4 : automated docking with selective receptor flexibility", J. Comput. Chem, 30, pp.2785~2791 (2009)
- Pierce LC, "Routine access to millisecond time scale events with accelerated molecular dynamics", J. Chem. Theory Comput, 8, pp.2997~3002 (2012)
- Götz AW, "Routine microsecond molecular dynamics simulations with AMBER on GPUs. 1. generalized born", J. Chem. Theory Comput, 8, pp.1542~1555 (2012)
- Salomon-Ferrer R, "Routine microsecond molecular dynamics simulations with AMBER on GPUs. 2. Explicit solvent particle Mesh Ewald", J. Chem. Theory Comput, 9, pp.3878~3888 (2013)
- Tam K, "Staphylococcus aureus secreted toxins and extracellular enzymes", Microbiol. Spectr, 7 (2019)
- Kong C, "Targeting Staphylococcus aureus toxins : a potential form of anti-virulence therapy", Toxins, 8, pp.72~ (2016)
- Gao Z, "Targeting staphylocoagulase with isoquercitrin protects mice from Staphylococcus aureus-induced pneumonia", Appl. Microbiol. Biotechnol, 104, pp.3909~3919 (2020)
- Boufridi A, "Harnessing the properties of natural products", Annu. Rev. Pharmacol. Toxicol, 58, pp.451~470 (2018)
- Zhang H, "Baicalein mediates protection against Staphylococcus aureus-induced pneumonia by inhibiting the coagulase activity of vWbp", Biochem. Pharmacol, 178, pp.114024~ (2020)
- Hwang SM, "Improved methods for detection and serotyping of coagulase from Staphylococcus aureus", Microbiol. Immunol, 33, pp.175~182 (1989)
