Abstract
Subtilosin A, a cyclic peptide from Bacillus subtilis is known for its antimicrobial activity against a diverse range of bacteria. Herein, we report the specific interaction between subtilosin A against virulent proteins of Aeromonas hydrophila through in silico analysis. Aeromonas toxic proteins such as aerolysin and hemolysin were selected from the non-redundant database. The hemolysin protein was designed by homology modelling tool, and it was validated using Ramachandran plot. Then subtilosin A and target toxin proteins were energy minimized for further docking study. The whole docking experiments were done using antibody mode in Cluspro. Subtilosin A building an active interaction with Aeromonas toxins through H-bonds and protein–protein docking analysis revealed that the hemolysin has 6 H-bond interaction towards the antimicrobial target protein subtilosin A than aerolysin, which has 9 H-bonds. The most favourable interacting residues of subtilosin A are Thr6, Cys13, Ile19, Pro20, Asp21, Phe22, Glu23 and Gly35 involving in the strong H-bond formation and proceeds to inhibition of toxin. Hence, the study confirmed that the subtilosin A has more antimicrobial activity to inhibit the Aeromonas toxins by interacting with their binding site residues for preventing extracellular cleavage.
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References
Abdel Monaim SA, Somboro AM, El-Faham A, de la Torre BG, Albericio F (2019) Bacteria hunt bacteria through an intriguing cyclic peptide. ChemMedChem 14(1):24–51. https://doi.org/10.1002/cmdc.201800597
Abrami L, van Der Goot FG (1999) Plasma membrane microdomains act as concentration platforms to facilitate intoxication by aerolysin. J Cell Biol 147:175–184. https://doi.org/10.1083/jcb.147.1.175
Aguilera-Arreola MG, Hernández-Rodríguez C, Zúñiga G, Figueras MJ, Castro-Escarpulli G (2005) Aeromonas hydrophila clinical and environmental ecotypes as revealed by genetic diversity and virulence genes. FEMS Microbiol Lett 242:231–240. https://doi.org/10.1016/j.femsle.2004.11.011
Arnold K, Bordoli L, Kopp J, Schwede T (2005) The SWISS-MODEL workspace: a web-based environment for protein structure homology modelling. Bioinformatics 22:195–201. https://doi.org/10.1093/bioinformatics/bti770
Arunkumar T, Vasuki KA, Narendrakumar G (2017) In silico analysis on docking studies of haemolysin protein in Vibrio Paraheamolyticus. Biomed Pharmacol J 10:1879–1886. https://doi.org/10.13005/bpj/1307
Babasaki K, Takao T, Shimonishi Y, Kurahashi K (1985) Subtilosin A, a new antibiotic peptide produced by Bacillus subtilis 168: isolation, structural analysis, and biogenesis. J Biochem 98:585–603. https://doi.org/10.1093/oxfordjournals.jbchem.a135315
Biscardi D, Castaldo A, Gualillo O, de Fusco R (2002) The occurrence of cytotoxic Aeromonas hydrophila strains in Italian mineral and thermal waters. Sci Total Environ 292:255–263. https://doi.org/10.1016/S0048-9697(01)01132-9
Craik DJ, Fairlie DP, Liras S, Price D (2013) The future of peptide-based drugs. Chem Biol Drug Des 81:136–147. https://doi.org/10.1111/cbdd.12055
Dobson A, Cotter PD, Ross RP, Hill C (2012) Bacteriocin production: a probiotic trait? Appl Environ Microbiol 78:1–6. https://doi.org/10.1128/AEM.05576-11
Dong J, Qiu J, Zhang Y, Lu C, Dai X, Wang J, Li H, Wang X, Tan W, Luo M, Niu X, Deng X (2013) Oroxylin A inhibits hemolysis via hindering the self-assembly of α-hemolysin heptameric transmembrane pore. PLoS Comput Biol 9:e1002869. https://doi.org/10.1371/journal.pcbi.1002869
Epple HJ, Mankertz J, Ignatius R, Liesenfeld O, Fromm M, Zeitz M, Chakraborty T, Schulzke JD (2004) Aeromonas hydrophila beta-hemolysin induces active chloride secretion in colon epithelial cells (HT-29/B6). Infect Immun 72:4848–4858. https://doi.org/10.1128/IAI.72.8.4848-4858.2004
Fields FO (1996) Use of bacteriocins in food: Regulatory considerations. J Food Prot 59:72–77. https://doi.org/10.4315/0362-028X-59.13.72
Fivaz M, Abrami L, Tsitrin Y, van der Goot FG (2001) Aerolysin from Aeromonas hydrophila and related toxins. In: van der Goot FG (ed) Pore-forming toxins. Springer, Berlin. https://doi.org/10.1007/978-3-642-56508-3_3
Geourjon C, Deléage G (1995) SOPMA: significant improvements in protein secondary structure prediction by consensus prediction from multiple alignments. Comput Appl Biosci 11:681–684. https://doi.org/10.1093/bioinformatics/11.6.681
Goebel W, Chakraborty T, Kreft J (1988) Bacterial hemolysins as virulence factors. Antonie Van Leeuwenhoek 54:453–463. https://doi.org/10.1007/BF00461864
Igbinosa IH, Igumbor EU, Aghdasi F, Tom M, Okoh AI (2012) Emerging Aeromonas species infections and their significance in public health. Sci World J 2012:625023. https://doi.org/10.1100/2012/625023
Kawulka KE, Sprules T, Diaper CM, Whittal RM, McKay RT, Mercier P, Zuber P, Vederas JC (2004) Structure of subtilosin A, a cyclic antimicrobial peptide from Bacillus subtilis with unusual sulfur to alpha-carbon cross-links: formation and reduction of alpha-thio-alpha-amino acid derivatives. Biochemistry 43(12):3385–3395. https://doi.org/10.1021/bi0359527
Kozakov D, Hall DR, Xia B, Porter KA, Padhorny D, Yueh C, Beglov D, Vajda S (2017) The ClusPro web server for protein–protein docking. Nat Protoc 12:255–278. https://doi.org/10.1038/nprot.2016.169
Kozińska A, Pękala A (2012) Characteristics of disease spectrum in relation to species, serogroups, and adhesion ability of motile Aeromonads in fish. Sci World J 2012:949358. https://doi.org/10.1100/2012/949358
Mathur H, Rea MC, Cotter PD, Hill C, Paul Ross R (2015) The sactibiotic subclass of bacteriocins: an update. Curr Protein Pept Sci 16:549–558. https://doi.org/10.2174/1389203716666150515124831
Montalbán-López M, Scott TA, Ramesh S, Rahman IR, van Heel AJ, Viel JH, Bandarian V, Dittmann E, Genilloud O, Goto Y, Grande Burgos MJ, Hill C, Kim S, Koehnke J, Latham JA, Link AJ, Martínez B, Nair SK, Nicolet Y, Rebuffat S, Sahl H-G, Sareen D, Schmidt EW, Schmitt L, Severinov K, Süssmuth RD, Truman AW, Wang H, Weng J-K, van Wezel GP, Zhang Q, Zhong J, Piel J, Mitchell DA, Kuipers OP, van der Donk WA (2020) New developments in RiPP discovery, enzymology and engineering. Nat Prod Rep 38:130–239. https://doi.org/10.1039/D0NP00027B
Nation RL, Li J (2009) Colistin in the 21st century. Curr Opin Infect Dis 22:535–543. https://doi.org/10.1097/QCO.0b013e328332e672
Olson R, Gouaux E (2005) Crystal structure of the Vibrio cholerae cytolysin (VCC) pro-toxin and its assembly into a heptameric transmembrane pore. J Mol Biol 350:997–1016. https://doi.org/10.1016/j.jmb.2005.05.045
Rani N, Saravanan V, Lakshmi PTV, Annamalai A (2014) Inhibition of pore formation by blocking the assembly of Staphylococcus aureus α-hemolysin through a novel peptide inhibitor: an in silico approach. Int J Pept Res Ther 20:575–583. https://doi.org/10.1007/s10989-014-9424-x
Rashidieh B, Etemadiafshar S, Memari G, Mirzaeichegeni M, Yazdi S, Farsimadan F, Alizadeh S (2015) A molecular modeling based screening for potential inhibitors to alpha hemolysin from Staphylococcus aureus. Bioinformation 11:373–377. https://doi.org/10.6026/97320630011373
Rasmussen-Ivey CR, Figueras MJ, McGarey D, Liles MR (2016) Virulence factors of Aeromonas hydrophila: in the wake of reclassification. Front Microbiol 7:1337. https://doi.org/10.3389/fmicb.2016.01337
Shelburne CE, An FY, Dholpe V, Ramamoorthy A, Lopatin DE, Lantz MS (2007) The spectrum of antimicrobial activity of the bacteriocin Subtilosin A. J Antimicrob Chemother 59:297–300. https://doi.org/10.1093/jac/dkl495
Simons A, Alhanout K, Duval RE (2020) Bacteriocins, antimicrobial peptides from bacterial origin: overview of their biology and their impact against multidrug-resistant bacteria. Microorganisms 8:639. https://doi.org/10.3390/microorganisms8050639
Stein T, Düsterhus S, Stroh A, Entian K-D (2004) Subtilosin production by two Bacillus subtilis subspecies and variance of the sbo-alb cluster. Appl Environ Microbiol 70:2349–2353. https://doi.org/10.1128/aem.70.4.2349-2353.2004
Thennarasu S, Lee D-K, Poon A, Kawulka KE, Vederas JC, Ramamoorthy A (2005) Membrane permeabilization, orientation, and antimicrobial mechanism of Subtilosin A. Chem Phys Lipids 137:38–51. https://doi.org/10.1016/j.chemphyslip.2005.06.003
Tian W, Chen C, Lei X, Zhao J, Liang J (2018) CASTp 3.0: computed atlas of surface topography of proteins. Nucleic Acids Res 46:W363–W367. https://doi.org/10.1093/nar/gky473
Torchala M, Moal IH, Chaleil RAG, Fernandez-Recio J, Bates PA (2013) SwarmDock: a server for flexible protein–protein docking. Bioinformatics 29:807–809. https://doi.org/10.1093/bioinformatics/btt038
Vignesh V, Sathiyanarayanan G, Parthiban K, Kumar KS, Thirumurugan R (2018) Functional assessment of Subtilosin A against Aeromonas spp. causing gastroenteritis and hemorrhagic septicaemia. Indian J Biotechnol 17:27–32
Vijai S, Pallavi S (2009) Inhibition of oligomerization of aerolysin from Aeromonas hydrophila: homology modeling and docking approach for exploration of hemorrhagic septicemia. Lett Drug Des Discov 6:215–223. https://doi.org/10.2174/157018009787847864
Vlieghe P, Lisowski V, Martinez J, Khrestchatisky M (2010) Synthetic therapeutic peptides: science and market. Drug Discov Today 15:40–56. https://doi.org/10.1016/j.drudis.2009.10.009
Wang G, Clark CG, Liu C, Pucknell C, Munro CK, Kruk TM, Caldeira R, Woodward DL, Rodgers FG (2003) Detection and characterization of the hemolysin genes in Aeromonas hydrophila and Aeromonas sobria by multiplex PCR. J Clin Microbiol 41:1048–1054. https://doi.org/10.1128/JCM.41.3.1048-1054.2003
Wang T, Zhang P, Lv H, Deng X, Wang J (2020) A natural dietary flavone myricetin as an α-hemolysin inhibitor for controlling Staphylococcus aureus infection. Front Cell Infect Microbiol 10:330. https://doi.org/10.3389/fcimb.2020.00330
Wong CYF, Heuzenroeder MW, Flower RLP (1998) Inactivation of two haemolytic toxin genes in Aeromonas hydrophila attenuates virulence in a suckling mouse model. Microbiology 144:291–298. https://doi.org/10.1099/00221287-144-2-291
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The authors are thankful to “RUSA, 2.0 - Biological Sciences, Bharathidasan University” and Yaazh Xenomics (www.yaazhxenomics.com), Chennai.
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Venkatasamy, V., Durairaj, R., Karuppaiah, P. et al. An In Silico Evaluation of Molecular Interaction Between Antimicrobial Peptide Subtilosin A of Bacillus subtilis with Virulent Proteins of Aeromonas hydrophila. Int J Pept Res Ther 27, 1709–1718 (2021). https://doi.org/10.1007/s10989-021-10203-1
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DOI: https://doi.org/10.1007/s10989-021-10203-1