Computational screening of antimicrobial peptides for Acinetobacter baumannii


Autoři: Ayan Majumder aff001;  Malay Ranjan Biswal aff001;  Meher K. Prakash aff001
Působiště autorů: Theoretical Science Unit, Jawaharlal Nehru Centre for Advanced Scientific Research, Jakkur, Bengaluru, India aff001
Vyšlo v časopise: PLoS ONE 14(10)
Kategorie: Research Article
doi: 10.1371/journal.pone.0219693

Souhrn

Acinetobacter baumannii, has been developing resistance to even the last line of drugs. Antimicrobial peptides (AMPs) to which bacteria do not develop resistance easily may be the last hope. A few independent experimental studies have designed and studied the activity of AMPs on A. baumannii, however the number of such studies are still limited. With the goal of developing a rational approach to the screening of AMPs against A. baumannii, we carefully curated the drug activity data from 75 cationic AMPs, all measured with a similar protocol, and on the same ATCC 19606 strain. A quantitative model developed and validated with a part of the data. While the model may be used for predicting the activity of any designed AMPs, in this work, we perform an in silico screening for the entire database of naturally occurring AMPs, to provide a rational guidance in this urgently needed drug development.

Klíčová slova:

Acinetobacter baumannii – Antimicrobial resistance – Antimicrobials – Artificial neural networks – Drug research and development – Neurons – Toxicity – Predictive toxicology


Zdroje

1. Nemec A, Musilek M, Maixnerova M, De Baere T, van der Reijden TJ, Vaneechoutte M, et al. Acinetobacter beijerinckii sp. nov. and Acinetobacter gyllenbergii sp. nov., haemolytic organisms isolated from humans. International Journal of Systematic and Evolutionary microbiology. 2009;59(1):118–124. https://dx.doi.org/10.1099/ijs.0.001230-0. 19126734

2. Towner K. Acinetobacter: an old friend, but a new enemy. Journal of Hospital Infection. 2009;73(4):355–363. doi: 10.1016/j.jhin.2009.03.032 19700220

3. Struelens M, Carlier E, Maes N, Serruys E, Quint WG, Van Belkum A. Nosocomial colonization and infection with multiresistant Acinetobacter baumannii: outbreak delineation using DNA macrorestriction analysis and PCR-fingerprinting. Journal of Hospital infection. 1993;25(1):15–32. doi: 10.1016/0195-6701(93)90005-k 7901273

4. Davis KA, Moran KA, McAllister CK, Gray PJ. Multidrug-resistant Acinetobacter extremity infections in soldiers. Emerging infectious diseases. 2005;11(8):1218–1224. doi: 10.3201/1108.050103 16102310

5. Young LS, Sabel AL, Price CS. Epidemiologic, clinical, and economic evaluation of an outbreak of clonal multidrug-resistant Acinetobacter baumannii infection in a surgical intensive care unit. Infection Control & Hospital Epidemiology. 2007;28(11):1247–1254.

6. Sievert DM, Ricks P, Edwards JR, Schneider A, Patel J, Srinivasan A, et al. Antimicrobial-resistant pathogens associated with healthcare-associated infections summary of data reported to the National Healthcare Safety Network at the Centers for Disease Control and Prevention, 2009–2010. Infection Control & Hospital Epidemiology. 2013;34(1):1–14.

7. Weiner LM, Webb AK, Limbago B, Dudeck MA, Patel J, Kallen AJ, et al. Antimicrobial-resistant pathogens associated with healthcare-associated infections: summary of data reported to the National Healthcare Safety Network at the Centers for Disease Control and Prevention, 2011–2014. Infection Control & Hospital Epidemiology. 2016;37(11):1288–1301.

8. Gordon NC, Wareham DW. Multidrug-resistant Acinetobacter baumannii: mechanisms of virulence and resistance. International Journal of Antimicrobial Agents. 2010;35(3):219–226. doi: 10.1016/j.ijantimicag.2009.10.024 20047818

9. Falagas ME, Karageorgopoulos DE. Pandrug resistance (PDR), extensive drug resistance (XDR), and multidrug resistance (MDR) among Gram-negative bacilli: need for international harmonization in terminology. Clinical Infectious Diseases. 2008;46(7):1121–1122. doi: 10.1086/528867 18444833

10. Pachón J, Vila J. Treatment of multiresistant Acinetobacter baumannii infections. Current Opinion in Investigational Drugs (London, England: 2000). 2009;10(2):150–156.

11. Öncül O, Keskin Ö, Acar HV, Küçükardalı Y, Evrenkaya R, Atasoyu EM, et al. Hospital-acquired infections following the 1999 Marmara earthquake. Journal of Hospital Infection. 2002;51(1):47–51. doi: 10.1053/jhin.2002.1205 12009820

12. Davies J, Davies D. Origins and evolution of antibiotic resistance. Microbiology and Molecular Biology Reviews. 2010;74(3):417–433. doi: 10.1128/MMBR.00016-10 20805405

13. Tan SYY, Chua SL, Liu Y, Høiby N, Andersen LP, Givskov M, et al. Comparative genomic analysis of rapid evolution of an extreme-drug-resistant Acinetobacter baumannii clone. Genome Biology and Evolution. 2013;5(5):807–818. doi: 10.1093/gbe/evt047 23538992

14. Hood MI, Mortensen BL, Moore JL, Zhang Y, Kehl-Fie TE, Sugitani N, et al. Identification of an Acinetobacter baumannii zinc acquisition system that facilitates resistance to calprotectin-mediated zinc sequestration. PLoS Pathogens. 2012;8(12):e1003068. doi: 10.1371/journal.ppat.1003068 23236280

15. Fournier PE, Vallenet D, Barbe V, Audic S, Ogata H, Poirel L, et al. Comparative genomics of multidrug resistance in Acinetobacter baumannii. PLoS Genetics. 2006;2(1):e7. doi: 10.1371/journal.pgen.0020007 16415984

16. Sahl JW, Gillece JD, Schupp JM, Waddell VG, Driebe EM, Engelthaler DM, et al. Evolution of a pathogen: a comparative genomics analysis identifies a genetic pathway to pathogenesis in Acinetobacter. PloS One. 2013;8(1):e54287. doi: 10.1371/journal.pone.0054287 23365658

17. Nemec A, Krizova L, Maixnerova M, van der Reijden TJ, Deschaght P, Passet V, et al. Genotypic and phenotypic characterization of the Acinetobacter calcoaceticus–Acinetobacter baumannii complex with the proposal of Acinetobacter pittii sp. nov.(formerly Acinetobacter genomic species 3) and Acinetobacter nosocomialis sp. nov.(formerly Acinetobacter genomic species 13TU). Research in Microbiology. 2011;162(4):393–404. doi: 10.1016/j.resmic.2011.02.006

18. Fan B, Guan J, Wang X, Cong Y. Activity of colistin in combination with meropenem, tigecycline, fosfomycin, fusidic acid, rifampin or sulbactam against extensively drug-resistant Acinetobacter baumannii in a murine thigh-infection model. PloS One. 2016;11(6):e0157757. doi: 10.1371/journal.pone.0157757 27315107

19. Kim WY, Moon JY, Huh JW, Choi SH, Lim CM, Koh Y, et al. Comparable efficacy of tigecycline versus colistin therapy for multidrug-resistant and extensively drug-resistant Acinetobacter baumannii pneumonia in critically ill patients. PLoS One. 2016;11(3):e0150642. doi: 10.1371/journal.pone.0150642 26934182

20. Rao GG, Ly NS, Diep J, Forrest A, Bulitta JB, Holden PN, et al. Combinatorial pharmacodynamics of polymyxin B and tigecycline against heteroresistant Acinetobacter baumannii. International Journal of Antimicrobial Agents. 2016;48(3):331–336. doi: 10.1016/j.ijantimicag.2016.06.006 27449542

21. Zasloff M. Antimicrobial peptides of multicellular organisms. Nature. 2002;415(6870):389–395. doi: 10.1038/415389a 11807545

22. Hancock RE, Sahl HG. Antimicrobial and host-defense peptides as new anti-infective therapeutic strategies. Nature Biotechnology. 2006;24(12):1551–1557. doi: 10.1038/nbt1267 17160061

23. Ghosh A, Kar RK, Jana J, Saha A, Jana B, Krishnamoorthy J, et al. Indolicidin targets duplex DNA: structural and mechanistic insight through a combination of spectroscopy and microscopy. ChemMedChem. 2014;9(9):2052–2058. doi: 10.1002/cmdc.201402215 25044630

24. Hao G, Shi YH, Tang YL, Le GW. The intracellular mechanism of action on Escherichia coli of BF2-A/C, two analogues of the antimicrobial peptide Buforin 2. Journal of microbiology. 2013;51(2):200–206.

25. Krizsan A, Volke D, Weinert S, Sträter N, Knappe D, Hoffmann R. Insect-Derived Proline-Rich Antimicrobial Peptides Kill Bacteria by Inhibiting Bacterial Protein Translation at the 70 S Ribosome. Angewandte Chemie International Edition. 2014;53(45):12236–12239. doi: 10.1002/anie.201407145 25220491

26. Seefeldt AC, Nguyen F, Antunes S, Pérébaskine N, Graf M, Arenz S, et al. The proline-rich antimicrobial peptide Onc112 inhibits translation by blocking and destabilizing the initiation complex. Nature structural & molecular biology. 2015;22(6):470.

27. Roy RN, Lomakin IB, Gagnon MG, Steitz TA. The mechanism of inhibition of protein synthesis by the proline-rich peptide oncocin. Nature structural & molecular biology. 2015;22(6):466.

28. Dangel A, Ackermann N, Abdel-Hadi O, Maier R, Önder K, Francois P, et al. A de novo-designed antimicrobial peptide with activity against multiresistant Staphylococcus aureus acting on RsbW kinase. The FASEB Journal. 2013;27(11):4476–4488. doi: 10.1096/fj.13-234575 23901070

29. Nguyen LT, Haney EF, Vogel HJ. The expanding scope of antimicrobial peptide structures and their modes of action. Trends in Biotechnology. 2011;29(9):464–472. doi: 10.1016/j.tibtech.2011.05.001 21680034

30. Yeaman MR, Yount NY. Mechanisms of antimicrobial peptide action and resistance. Pharmacological Reviews. 2003;55(1):27–55. doi: 10.1124/pr.55.1.2 12615953

31. Brogden KA. Antimicrobial peptides: pore formers or metabolic inhibitors in bacteria? Nature Reviews Microbiology. 2005;3(3):238–250. doi: 10.1038/nrmicro1098 15703760

32. Lohner K, Blondelle S. Molecular mechanisms of membrane perturbation by antimicrobial peptides and the use of biophysical studies in the design of novel peptide antibiotics. Combinatorial Chemistry & High Throughput Screening. 2005;8(3):241–256.

33. Jenssen H, Hamill P, Hancock RE. Peptide antimicrobial agents. Clinical microbiology reviews. 2006;19(3):491–511. doi: 10.1128/CMR.00056-05 16847082

34. Yeung AT, Gellatly SL, Hancock RE. Multifunctional cationic host defence peptides and their clinical applications. Cellular and Molecular Life Sciences. 2011;68(13):2161. doi: 10.1007/s00018-011-0710-x 21573784

35. Oyston P, Fox M, Richards S, Clark G. Novel peptide therapeutics for treatment of infections. Journal of Medical Microbiology. 2009;58(8):977–987. doi: 10.1099/jmm.0.011122-0 19528155

36. Poole K. Overcoming multidrug resistance in gram-negative bacteria. Current Opinion in Investigational Drugs (London, England: 2000). 2003;4(2):128–139.

37. Guaní-Guerra E, Santos-Mendoza T, Lugo-Reyes SO, Terán LM. Antimicrobial peptides: general overview and clinical implications in human health and disease. Clinical Immunology. 2010;135(1):1–11. doi: 10.1016/j.clim.2009.12.004 20116332

38. Jenssen H, Fjell CD, Cherkasov A, Hancock RE. QSAR modeling and computer-aided design of antimicrobial peptides. Journal of Peptide Science: An Official Publication of the European Peptide Society. 2008;14(1):110–114.

39. Sayiner HS, Abdalrahm AA, Basaran MA, Kovalishyn V, Kandemirli F. The Quantum Chemical and QSAR Studies on Acinetobacter Baumannii Oxphos Inhibitors. Medicinal Chemistry. 2018;14(3):253–268. doi: 10.2174/1573406413666171002124408 28969576

40. Wikler MA. Methods for dilution antimicrobial susceptibility tests for bacteria that grow aerobically: approved standard. Clinical and Laboratory Standards Institute. 2006.

41. Zhao L, Wang W, Sedykh A, Zhu H. Experimental errors in QSAR modeling sets: What we can do and what we cannot do. ACS omega. 2017;2(6):2805–2812. doi: 10.1021/acsomega.7b00274 28691113

42. Vila-Farres X, De La Maria CG, López-Rojas R, Pachón J, Giralt E, Vila J. In vitro activity of several antimicrobial peptides against colistin-susceptible and colistin-resistant Acinetobacter baumannii. Clinical Microbiology and Infection. 2012;18(4):383–387. doi: 10.1111/j.1469-0691.2011.03581.x

43. Peng SY, You RI, Lai MJ, Lin NT, Chen LK, Chang KC. Highly potent antimicrobial modified peptides derived from the Acinetobacter baumannii phage endolysin LysAB2. Scientific reports. 2017;7(1):11477. doi: 10.1038/s41598-017-11832-7 28904355

44. Jayamani E, Rajamuthiah R, Larkins-Ford J, Fuchs BB, Conery AL, Vilcinskas A, et al. Insect-derived cecropins display activity against Acinetobacter baumannii in a whole-animal high-throughput Caenorhabditis elegans model. Antimicrobial agents and chemotherapy. 2015; p. 1728–1737. doi: 10.1128/AAC.04198-14 25583713

45. Jaśkiewicz M, Neubauer D, Kazor K, Bartoszewska S, Kamysz W. Antimicrobial activity of selected antimicrobial peptides against planktonic culture and biofilm of Acinetobacter baumannii. Probiotics and Antimicrobial Proteins. 2018; p. 1–8.

46. Mohamed MF, Brezden A, Mohammad H, Chmielewski J, Seleem MN. A short D-enantiomeric antimicrobial peptide with potent immunomodulatory and antibiofilm activity against multidrug-resistant Pseudomonas aeruginosa and Acinetobacter baumannii. Scientific Reports. 2017;7(1):6953. doi: 10.1038/s41598-017-07440-0 28761101

47. Andrä J, Monreal D, de Tejada GM, Olak C, Brezesinski G, Gomez SS, et al. Rationale for the design of shortened derivatives of the NK-lysin derived antimicrobial peptide NK-2 with improved activity against Gram-negative pathogens. Journal of Biological Chemistry. 2007. doi: 10.1074/jbc.M608920200

48. Kohn EM, Shirley DJ, Arotsky L, Picciano AM, Ridgway Z, Urban MW, et al. Role of cationic side chains in the antimicrobial activity of C18G. Molecules. 2018;23(2):329.

49. Li D, Yang Y, Tian Z, Lv J, Sun F, Wang Q, et al. Synergistic antibiotic effect of looped antimicrobial peptide CLP-19 with bactericidal and bacteriostatic agents. Oncotarget. 2017;8(34):55958–55966. doi: 10.18632/oncotarget.18124 28915566

50. Almaaytah A, Ya’u A, Abualhaijaa A, Tarazi S, Alshar’i N, Al-Balas Q. Peptide consensus sequence determination for the enhancement of the antimicrobial activity and selectivity of antimicrobial peptides. Infection and drug resistance. 2017;10:1–17. doi: 10.2147/IDR.S118877 28096686

51. Thomsen TT. Peptide Antibiotics for ESKAPE Pathogens: Past, Present and Future Perspectives of Antimicrobial Peptides for the Treatment of Serious Gram-Negative and Gram-Positive Infections. Department of Biology, Faculty of Science, University of Copenhagen; 2016.

52. Almaaytah A, Qaoud MT, Abualhaijaa A, Al-Balas Q, Alzoubi KH. Hybridization and antibiotic synergism as a tool for reducing the cytotoxicity of antimicrobial peptides. Infection and Drug Resistance. 2018;11:835–847. doi: 10.2147/IDR.S166236 29910626

53. Conchillo-Solé O, de Groot NS, Avilés FX, Vendrell J, Daura X, Ventura S. AGGRESCAN: a server for the prediction and evaluation of “hot spots” of aggregation in polypeptides. BMC Bioinformatics. 2007;8(1):65. doi: 10.1186/1471-2105-8-65

54. Fernandez-Escamilla AM, Rousseau F, Schymkowitz J, Serrano L. Prediction of sequence-dependent and mutational effects on the aggregation of peptides and proteins. Nature Biotechnology. 2004;22(10):1302–1306. doi: 10.1038/nbt1012 15361882

55. Ikai A. Thermostability and aliphatic index of globular proteins. The Journal of Biochemistry. 1980;88(6):1895–1898. 7462208

56. Kyte J, Doolittle RF. A simple method for displaying the hydropathic character of a protein. Journal of Molecular Biology. 1982;157(1):105–132. doi: 10.1016/0022-2836(82)90515-0 7108955

57. Gautier R, Douguet D, Antonny B, Drin G. HELIQUEST: a web server to screen sequences with specific α-helical properties. Bioinformatics. 2008;24(18):2101–2102. doi: 10.1093/bioinformatics/btn392

58. Gupta S, Kapoor P, Chaudhary K, Gautam A, Kumar R, Raghava GP, et al. In silico approach for predicting toxicity of peptides and proteins. PLoS One. 2013;8(9):e73957. doi: 10.1371/journal.pone.0073957 24058508

59. Pedregosa F, Varoquaux G, Gramfort A, Michel V, Thirion B, Grisel O, et al. Scikit-learn: Machine learning in Python. Journal of Machine Learning Research. 2011;12(Oct):2825–2830.

60. Wang Z, Wang G. APD: the antimicrobial peptide database. Nucleic Acids Research. 2004;32(suppl_1):D590–D592. doi: 10.1093/nar/gkh025 14681488

61. Wang G, Li X, Wang Z. APD2: the updated antimicrobial peptide database and its application in peptide design. Nucleic Acids Research. 2008;37(suppl_1):D933–D937. doi: 10.1093/nar/gkn823 18957441

62. Wang G, Li X, Wang Z. APD3: the antimicrobial peptide database as a tool for research and education. Nucleic Acids Research. 2015;44(D1):D1087–D1093. doi: 10.1093/nar/gkv1278 26602694

63. Shai Y. Mode of action of membrane active antimicrobial peptides. Peptide Science: Original Research on Biomolecules. 2002;66(4):236–248.

64. Deslouches B, Phadke SM, Lazarevic V, Cascio M, Islam K, Montelaro RC, et al. De novo generation of cationic antimicrobial peptides: influence of length and tryptophan substitution on antimicrobial activity. Antimicrobial Agents and Chemotherapy. 2005;49(1):316–322. doi: 10.1128/AAC.49.1.316-322.2005 15616311

65. Oren Z, Lerman JC, Gudmundsson GH, Agerberth B, Shai Y. Structure and organization of the human antimicrobial peptide LL-37 in phospholipid membranes: relevance to the molecular basis for its non-cell-selective activity. Biochemical Journal. 1999;341(Pt 3):501–513. 10417311

66. Kustanovich I, Shalev DE, Mikhlin M, Gaidukov L, Mor A. Structural requirements for potent versus selective cytotoxicity for antimicrobial dermaseptin S4 derivatives. Journal of Biological Chemistry. 2002;277(19):16941–16951. doi: 10.1074/jbc.M111071200 11847217

67. Feder R, Dagan A, Mor A. Structure-activity relationship study of antimicrobial dermaseptin S4 showing the consequences of peptide oligomerization on selective cytotoxicity. Journal of Biological Chemistry. 2000;275(6):4230–4238. doi: 10.1074/jbc.275.6.4230 10660589

68. Ehrenstein G, Lecar H. Electrically gated ionic channels in lipid bilayers. Quarterly reviews of biophysics. 1977;10(1):1–34. 327501

69. Majumder A, Biswal MR, Prakash MK. One drug multiple targets: An approach to predict drug efficacies on bacterial strains differing in membrane composition. ACS Omega. 2019;4(3):4977–4983.

70. Mishra NN, McKinnell J, Yeaman MR, Rubio A, Nast CC, Chen L, et al. In vitro cross-resistance to daptomycin and host defense cationic antimicrobial peptides in clinical methicillin-resistant Staphylococcus aureus isolates. Antimicrobial agents and chemotherapy. 2011;55(9):4012–4018. doi: 10.1128/AAC.00223-11 21709105

71. das Neves RC, Mortari MR, Schwartz EF, Kipnis A, Junqueira-Kipnis AP. Antimicrobial and Antibiofilm Effects of Peptides from Venom of Social Wasp and Scorpion on Multidrug-Resistant Acinetobacter baumannii. Toxins. 2019;11(4):216.

72. Hirsch R, Wiesner J, Marker A, Pfeifer Y, Bauer A, Hammann PE, et al. Profiling antimicrobial peptides from the medical maggot Lucilia sericata as potential antibiotics for MDR Gram-negative bacteria. Journal of Antimicrobial Chemotherapy. 2018;74(1):96–107.

73. Di Bonaventura I, Baeriswyl S, Capecchi A, Gan BH, Jin X, Siriwardena TN, et al. An antimicrobial bicyclic peptide from chemical space against multidrug resistant Gram-negative bacteria. Chemical communications. 2018;54(40):5130–5133. doi: 10.1039/c8cc02412j 29717727


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