Publicación:
Diseño, síntesis, caracterización y evaluación in vitro de la actividad de los péptidos antimicrobianos contra bacterias patógenas resistentes a antibióticos

dc.contributor.authorOrtiz López, Claudia
dc.contributor.corporatenameAcademia Colombiana de Ciencias Exactas, Físicas y Naturalesspa
dc.date.accessioned2021-12-09T23:47:28Z
dc.date.available2021-12-09T23:47:28Z
dc.date.issued2019-12-20
dc.description.abstractLos péptidos antimicrobianos han atraído mucha atención como nuevos agentes terapéuticos contra enfermedades infecciosas. En este estudio se hizo el diseño racional in silico de 18 péptidos catiónicos con actividad antimicrobiana contra bacterias patógenas resistentes utilizando el programa DEPRAMP desarrollado en el Grupo de Investigación en Bioquímica y Microbiología de la Universidad Industrial de Santander. Posteriormente, los péptidos diseñados se sintetizaron en fase sólida con el método de 9-fluorenilmetoxicarbonilo en medio ácido. Se obtuvieron secuencias cortas de 17 aminoácidos con un grado de pureza entre 95 y 98 %, estructura secundaria de hélice alfa, carga neta catiónica (entre +3 y +6), punto isoeléctrico entre 10,04 y 12,03 e índice de hidropatía entre -0,62 y 1,14. Todos los péptidos antimicrobianos mostraron actividad antibacteriana y bactericida in vitro frente al menos una de las cepas patógenas estudiadas: Escherichia coli O157: H7, Pseudomonas aeruginosa y Staphylococcus aureus resistente a la meticilina. Los péptidos antimicrobianos GIBIM-P5S9K y GIBIM-P5F8W registraron la mejor actividad antibacteriana, alcanzando una concentración mínima inhibitoria (CMI 99) en rangos de 0,5 a 25 μM frente a las tres cepas evaluadas, de las cuales Escherichia coli O157: H7 fue la más sensible frente al péptido antimicrobiano GIBIMP5F8W, con una CMI 99 de 0,5 μM y una concentración mínima bactericida de 10 μM, en tanto que la cepa de Pseudomonas aeruginosa fue la más resistente, con una CMI de más de 100 μM frente a más de cinco péptidos antimicrobianos. La toxicidad de los péptidos sobre los eritrocitos produjo un porcentaje de hemólisis menor al 40 % en concentraciones de 50 μM. Por su parte, en las líneas celulares de carcinoma de pulmón A549 y HepG2, el único compuesto que presentó toxicidad fue GIBIM-P5F8W, presentando un 36% de células viables en concentraciones de 100 μM del péptido en la línea celular A549.spa
dc.description.abstractAntimicrobial peptides have attracted much attention as new therapeutic agents against infectious diseases. In this work, we made the rational in silico design of 18 cationic peptides with antimicrobial activity against resistant pathogenic bacteria using the DEPRAMP software developed in the GIBIM research group. Subsequently, the designed peptides were synthesized in solid phase using the Fmoc strategy in an acid medium. Then, sequences of 17 amino acids were obtained with a degree of purity between 95 and 98%, secondary structure α-helix, net cationic charge (between +3 and +6), pI between 10.04 to 12.03, and hydropathy index between -0.62 and 1.14. All antimicrobial peptides showed antibacterial and bactericidal activity in vitro against at least one of the pathogenic strains studied: Escherichia coli O157: H7, Pseudomonas aeruginosa, and Staphylococcus aureus Resistant to Methicillin. The GIBIM-P5S9K and GIBIM-P5F8W antimicrobial peptides presented the best antibacterial activities reaching MIC99 in ranges of 0.5 to 25 μM against the three strains evaluated. E. coli O157: H7 was the most sensitive strain to the GIBIMP5F8W presenting 0.5 μM MIC99 and 10 μM MBC, and P. aeruginosa was the most resistant strain with MIC values over 100 μM against more than five antimicrobial peptides. The toxicity of peptides in erythrocytes produced a hemolysis percentage of less than 40% in concentrations of 50 μM. On the other hand, in the lung carcinoma cell lines A549 and HepG2, the only compound that presented toxicity was GIBIM-P5F8W, presenting 36% of viable cells in concentrations of 100 μM of the peptide in the A549 cell line.eng
dc.format.mimetypeapplication/pdfspa
dc.identifier.doihttps://doi.org/10.18257/raccefyn.864
dc.identifier.urihttps://repositorio.accefyn.org.co/handle/001/1167
dc.language.isospaspa
dc.publisherAcademia Colombiana de Ciencias Exactas, Físicas y Naturalesspa
dc.publisher.placeBogotá, Colombiaspa
dc.relation.citationendpage627spa
dc.relation.citationissue169spa
dc.relation.citationstartpage614spa
dc.relation.citationvolume43spa
dc.relation.ispartofjournalRevista de la Academia Colombiana de Ciencias Exactas, Físicas y Naturalesspa
dc.rightsCreative Commons Attribution-NonCommercial-ShareAlike 4.0 Internationalspa
dc.rights.accessrightsinfo:eu-repo/semantics/openAccessspa
dc.rights.coarhttp://purl.org/coar/access_right/c_abf2spa
dc.rights.licenseAtribución-NoComercial 4.0 Internacional (CC BY-NC 4.0)spa
dc.rights.urihttps://creativecommons.org/licenses/by-nc/4.0/spa
dc.sourceRevista de la Academia Colombiana de Ciencias Exactas, Físicas y Naturalesspa
dc.subject.proposalPéptidos antimicrobianosspa
dc.subject.proposalAntimicrobial peptideseng
dc.subject.proposalResistencia microbianaspa
dc.subject.proposalMicrobial resistanceeng
dc.subject.proposalactividad antimicrobianaspa
dc.subject.proposalAntimicrobial activityeng
dc.titleDiseño, síntesis, caracterización y evaluación in vitro de la actividad de los péptidos antimicrobianos contra bacterias patógenas resistentes a antibióticosspa
dc.typeArtículo de revistaspa
dc.type.coarhttp://purl.org/coar/resource_type/c_6501spa
dc.type.coarversionhttp://purl.org/coar/version/c_970fb48d4fbd8a85spa
dc.type.contentDataPaperspa
dc.type.driverinfo:eu-repo/semantics/articlespa
dc.type.redcolhttp://purl.org/redcol/resource_type/ARTspa
dc.type.versioninfo:eu-repo/semantics/publishedVersionspa
dcterms.audienceEstudiantes, Profesores, Comunidad científica colombianaspa
dcterms.referencesAbercrombie, J. J., Leung, K. P., Chai, H., Hicks, R. P. (2015). Bioorganic & Medicinal Chemistry Spectral and biological evaluation of a synthetic antimicrobial peptide derived from 1-aminocyclohexane carboxylic acid. Bioorganic & Medicinal Chemistry. 23 (6):1341-1347spa
dcterms.referencesAguilar, M. (2004). HPLC of Peptides and Proteins: Methods and Protocols, Human press. Totowa, New Jersey, United States p. 251spa
dcterms.referencesAndersson, D. I., Hughes, D., Kubicek-Sutherland, J. Z. (2016). Mechanisms and consequences of bacterial resistance to antimicrobial peptides. Drug Resist. Updat. 26: 43-57spa
dcterms.referencesAoki W & Ueda M. (2013). Characterization of antimicrobial peptides toward the development of novel antibiotics. Pharmaceuticals. 6: 1055-1081spa
dcterms.referencesBabu, V. V. S. & Gopi, H. N. (1998). Rapid and efficient synthesis of peptide fragments containing α-Aminoisobutyric acid using Fmoc-amino acid chlorides / potassium salt of 1-Hydroxybenzotriazole. 39: 1049-050spa
dcterms.referencesBakshi, K., Liyanage, M., Volkin, D., Middaugh, C. (2014). Circular dichroism of peptides, Methods Mol. Biol. 1088: 247-253spa
dcterms.referencesBerthold, N., Czihal, P., Fritsche, S., Sauer, U., Schiffer, G., Knappe, D., Alber, G., Hoffmann, R. (2013). Novel apidaecin 1b analogs with superior serum stabilities for treatment of infections by Gram-negative pathogens, Antimicrob. Agents Chemother. 57: 402-409spa
dcterms.referencesBroekman, D. C., Frei, D. M., Gylfason, G. A., Steinarsson, A., Jörnvall, H., Agerberth, B., Maier, V. H. (2011). Cod cathelicidin: Isolation of the mature peptide, cleavage site characterisation and developmental expression. Develop-mental and Comparative Immunology. 35 (3): 296-303spa
dcterms.referencesBrogan, D. M. & Mossialos, E. (2016). A critical analysis of the review on antimicrobial resistance report and the infec-tious disease financing facility, Global. Health. 12: 1-7.spa
dcterms.referencesChan, D. I., Prenner, E. J., Vogel, H. J. (2006). Tryptophan- and arginine-rich antimicrobial peptides: Structures and mechanisms of action. Biochim. Biophys. Acta. 1758:1184-1202spa
dcterms.referencesChaudhary, A. S. (2016). A review of global initiatives to fight antibiotic resistance and recent antibiotic’s discovery, Acta Pharm. Sin. B. 6: 552-556spa
dcterms.referencesChen, Y., Mant, C. T., Farmer, S. W., Hancock, R. E. W., Vasil, M. L., Hodges, R.S. (2005). Rational Design of alpha-Helical Antimicrobial Peptides with Enhanced Activities and Specificity/Therapeutic Index, J Biol.Chem. 280: 12316-12329.spa
dcterms.referencesConlon, J. M., Mechkarska, M., Coquet, L., Jouenne, T., Leprince, J., Vaudry, H., King, J. D. (2011). Peptides characterization of antimicrobial peptides in skin secretions from discrete populations of Lithobates chiricahuensis(Ranidae) from central and southern Arizona. Peptides. 32(4): 664-669.spa
dcterms.referencesCruz, J., Ortiz, C., Guzmán, F., Fernández-Lafuente, R., Torres, R. (2014). Antimicrobial peptides: Promising compounds against pathogenic microorganisms. Curr Med Chem. 21 (20): 2299-321.spa
dcterms.referencesCruz, J., Flórez, J., Torres, R., Urquiza, M., Gutiérrez, J. A., Guzmán, F., Ortiz, C. (2017). Antimicrobial activity of a new synthetic peptide loaded in polylactic acid or Poly(lactic-co-glycolic) acid nanoparticles against Pseudomonas aeruginosa, Escherichia coli O157:H7 and methicillin resistant Staphylococcus aureus (MRSA). Nanotechnology. 28 (13): 5102.spa
dcterms.referencesCruz J, Rondón-Villareal P., Torres R., Urquiza M., Álvarez C., Abengózar MA., Sierra D., Rivas L., Fernández-Lafuente R., Ortiz C. (2018) Design of bactericidal peptides against Escherichia coli O157:H7, Pseudomonas aeruginosa and methicillin-resistant Staphylococcus aureus. Medicinal Chemistry. 14: 1-12spa
dcterms.referencesDanial, M.; van Dulmen, T.H.; Aleksandrowicz, J.; Pötgens, A.J.; Klok, H.A. (2012). Site-specific PEGylation of HR2 peptides: Effects of PEG conjugation position and chain length on HIV-1 membrane fusion inhibition and proteolytic degradation. Bioconjug. Chem. 23: 1648-1660spa
dcterms.referencesDanial, M.; van Dulmen, T.H.; Aleksandrowicz, J.; Pötgens, A.J.; Klok, H.A. (2012). Site-specific PEGylation of HR2 peptides: Effects of PEG conjugation position and chain length on HIV-1 membrane fusion inhibition and proteolytic degradation. Bioconjug. Chem. 23: 1648-1660spa
dcterms.referencesFernández-Reyes, M., Díaz, D., de la Torre, B. G., Cabrales-Rico, A., Vallès- Miret, M., Jiménez-Barbero, J., Andreu, D., Rivas, L. (2010). Lysine Nε-Trimethylation, a Tool for Improving, J. Med. Chem. 53: 5587-5596spa
dcterms.referencesHouston, M. E., Jr., Kondejewski, L.H., Karunaratne, D.N., Gough, M., Fidai, S., Hodges, R.S., Hancock, R.E. (1998). Influence of preformed alpha-helix and alpha-helix induction on the activity of cationic an- timicro- bial peptides. J. Pept. Res. 52: 81-88spa
dcterms.referencesIl’ina, A.P., Kulikova, O. G., Maltsev, D. I., Krasnov, M. S., Rybakova, E., Skripnikova, V. S., Kuznetsova, E. S., Buryak, A. K., Yamskova, V. P., Yamskov, A. (2011). MALDI-TOF mass spectrometric identification of novel intercellular space peptides, Appl. Biochem. Microbiol. 47: 118-122spa
dcterms.referencesJaradat, D.M.M. (2018) Thirteen decades of peptide synthesis: Key developments in solid phase peptide synthesis and amide bond formation utilized in peptide ligation. Amino Acids. 50 (1): 39-68. Doi: 10.1007/s00726-017-2516-0spa
dcterms.referencesJenssen, H., Hamill, P., Hancock, R.E.W. (2006). Peptide anti-microbial agents, Clin. Microbiol. Rev. 19: 491-511.spa
dcterms.referencesJofré, C., Guzmán, F., Cárdenas, C., Albericio, F., Marshall, S.H.(2011) A natural peptide and its variants derived from the processing of infectious pancreatic necrosis virus (IPNV) dis-playing enhanced antimicrobial activity: A novel alternative for the control of bacterial diseases. Peptides. 32: 852-858spa
dcterms.referencesJoo, H.S., Fu, C.I., Otto, M. (2016) Bacterial Strategies of Resistance to Antimicrobial Peptides, Philos Trans R Soc Lond B Biol Sci. 371: 20150292.spa
dcterms.referencesKandasamy, S. K. & Larson, R. G. (2006). Effect of salt on the interactions of antimicrobial peptides with zwitterionic lipid bilayers, Biochim. Biophys. Acta - Biomembr. 1758:1274-1284spa
dcterms.referencesKim, J. Y., Park, S. C., Yoon, M. Y., Hahm, K. S., Park, Y.(2011). C-terminal amidation of PMAP-23: Translocation to the inner membrane of Gram-negative bacteria, Amino Acids. 40: 183-195.spa
dcterms.referencesKim, J.S., Joeng, J. H., Kim, Y. (2017) Design, Characterization, and Antimicrobial Activity of a Novel Antimicrobial Peptide Derived from Bovine Lactophoricin. J Microbiol Biotechnol. 27: 759-767.spa
dcterms.referencesKumar P., Kizhakkedathu J.N., Straus S. (2018). Antimicrobial Peptides: Diversity, Mechanism of Action and Strategies to Improve the Activity and Biocompatibility In Vivo. Biomacromolecules. 8 (1): 4spa
dcterms.referencesLee, S.H., Kim, S.J., Lee, Y.S., Song, M.D., Kim, I.H., Won, H.S. (2011). De novo generation of short antimicrobial peptides with simple amino acid composition. Regul. Pept. 166: 36-41spa
dcterms.referencesLee, J.K., Park, S.C., Hahm, K.S., Park, Y. (2013). Antimicrobial HPA3NT3 peptide analogs: Placement of aromatic rings and positive charges are key determinants for cell selectivity and mechanism of action. Biochim. Biophys. Acta. 1828: 443-54.spa
dcterms.referencesLi, B., Webster, T. J. (2018). Bacteria antibiotic resistance: New challenges and opportunities for implant-associated orthopedic infections. J Orthopaedic Res. 36 (1): 22-32. doi:10.1002/jor.23656spa
dcterms.referencesLi Y, Xiang Q, Zhang Q, Huang Y, Su Z. (2012). Overview on the recent study of antimicrobial peptides: Origins, functions, relative mechanisms and application. Peptides. 37 (2): 207-15. Doi: 10.1016/j.peptides.2012.07.001spa
dcterms.referencesLi, J., Koh, J. J., Liu, S., Lakshminarayanan, R., Verma, C. S., Beuerman, R. W. (2017). Membrane Active Antimicrobial Peptides: Translating Mechanistic Insights to Design. Frontiers in Neuroscience. 11: 73. Doi: 10.3389/fnins.2017.00073spa
dcterms.referencesLohner, K. (2001). The role of membrane lipid composition in cell targeting of antimicrobial peptides. In: Development of Novel Antimicrobial Agents: Emerging Strategies, Lohner, K. (Editor). Horizon Scientific Press: Wymondham, Norfolk, p. 149-165spa
dcterms.referencesLozano, D., Díaz, L., Echeverry, M., Pineda, S., Máttar, S. (2010). Staphylococcus aureus resistentes a meticilina (SARM) posi-tivos para PVL aislados en individuos sanos de Montería-Córdoba, Universitas Scientiarum. 1352: 159-165spa
dcterms.referencesMalik, E., Dennison, S. R., Harris, F., Phoenix, D. A. (2016). pH Dependent Antimicrobial Peptides and Proteins, Their Mechanisms of Action and Potential as Therapeutic Agents. Pharmaceuticals (Basel, Switzerland). 9 (4): 67. doi:10.3390/ph9040067spa
dcterms.referencesMathur, P. & Singh, S. (2013). Multidrug resistance in bacteria: A serious patient safety challenge for India. Journal of Laboratory Physicians. 5 (1): 5-10spa
dcterms.referencesMerlino, F., Carotenuto, A., Casciaro, B., Martora, F., Loffredo, M. R. , Di Grazia, A., Yousif, A. M., Brancaccio, D., Palomba, L., Novellino, E., Galdiero, M., Iovene, M.R., Mangoni, M.L., Grieco, P. (2017). Glycine-replaced derivatives of [Pro 3 ,DLeu 9 ]TL, a temporin L analogue: Evaluation of antimicrobial, cytotoxic and hemolytic activities, Eur. J. Med. Chem. 139: 750-761spa
dcterms.referencesNakhjavani, M., Zarghi, A., H Shirazi, F. (2014). Cytotoxicity of selected novel chalcone derivatives on human breast, lung and hepatic carcinoma cell lines, Iran. J. Pharm. Res. IJPR. 13: 953-958spa
dcterms.referencesNiederman, M. S. (2001). Impact ofantibiotic resistance on clinical outcomes and the cost of care. Crit. Care Med. 29: N114-20spa
dcterms.referencesOh,D., Sun, J., Nasrolahi-Shirazi, A., LaPlante, K.L., Rowley, D.C, Parang, K. (2014). Antibacterial Activities of Amphi-philic Cyclic Cell-Penetrating Peptides against Multidrug Resistant Pathogens, Mol. Pharm. 5: 161-171spa
dcterms.referencesPfalzgraff, A., Brandenburg, K., Weindl, G. (2018). Anti-microbial Peptides and Their Therapeutic Potential for Bacterial Skin Infections and Wounds. Front Pharmacol. 9: 281-304.spa
dcterms.referencesPrada, Y. A., Guzmán, F., Rondón, P., Escobar, P., Ortiz, C., Sierra, A., Torres, R., Mejía-Ospino, E. (2016). A New Synthetic Peptide with In vitro Antibacterial Potential Against Escherichia coli O1 57:H7 and Methicillin-Resistant Staphylococcus aureus (MRSA). Probiotics & Antimicro. Prot. 8: 134-140spa
dcterms.referencesReuken, P. A., Torres, D., Baier, M., Löffler, B., Lübbert, C., Lippmann, N., Stallmach, A., Bruns, T. (2017). Risk Factors for Multi-Drug Resistant Pathogens and Failure of Empiric First-Line Therapy in Acute Cholangitis. PloS one. 12 (1): e0169900. Doi: 10.1371/journal.pone.0169900spa
dcterms.referencesRozek, A., Powers, J.P., Friedrich, C.L., Hancock, R.E. (2003). Structure- based design of an indolicidin peptide analog with increased protease stability. Biochemistry. 42: 14130-14138spa
dcterms.referencesSchibli, D. J., Epand, R. F., Vogel, H. J. Epand, R. M. (2002). Tryptophan-rich antimicrobial peptides: Comparative properties and membrane interactions. Biochem. Cell Biol. 80: 667-677spa
dcterms.referencesSengupta, D., Leontiadou, H., Mark, A.E., Marrink, S. J.(2008). Toroidal pores formed by antimicrobial peptides show significant disorder. Biochim. Biophys. Acta. 1778: 2308-2317spa
dcterms.referencesShai, Y. (2002). Mode of Action of Membrane Active Antimicrobial Peptides, Biopolymers. 66: 236-248spa
dcterms.referencesSchmidt, C. (2017) Living in a microbial world. Nature Bio-technology. 35 (5): 401-403.spa
dcterms.referencesStrateva, T. & Yordanov, D. (2009). Pseudomonas aeruginosa – a phenomenon of bacterial resistance, J. Med. Microbiol. 58: 1133-1148.spa
dcterms.referencesavares, L. S. , Rettore, J. V. , Freitas, R. M., Porto, W. F., Duque, A. P. Singulani, Jde L, Silva, O. N., Detoni, Mde L, Vasconcelos, E. G., Dias, S. C., Franco, O. L., Santos, M de O. (2012). Antimicrobial activity of recombinant Pg-AMP1, a glycine-rich peptide from guava seeds. Peptides. 37: 294-300spa
dcterms.referencesTeixeira, V., Feio, M. J., Bastos, M. (2012). Role of lipids in the interaction of antimicrobial peptides with membranes. Prog. Lipid Res. 51: 149-177spa
dcterms.referencesTennessen J. A. & Blouin, M. S. (2010). A revised leopard frog phylogeny allows a more detailed examination of adaptive evolution at ranatuerin-2 antimicrobial peptide loci. Immunogenetics. 62: 333-343spa
dcterms.referencesTossi A, Sandri L, Giangaspero A. (2000). Amphipathic, a helical antimicrobial peptides activity. Biopolymers. 55: 4-30spa
dcterms.referencesTrindade, F., Amado, F., Pinto, J., Ferreira, R., Maia, C., Henriques, I., Vitorino, R. (2014). ScienceDirect Salivary peptidomic as a tool to disclose new potential antimicrobial peptides. Journal of Proteomics. 115: 49-57spa
dcterms.referencesTripathi, A. K., Kumari, T., Harioudh, M. K., Yadav, P. K., Kathuria, M., Shukla, P.K., Mitra, K., Ghosh, J. K.(2017) Identification of GXXXXG motif in Chrysophsin-1 and its implication in the design of analogs with cell-selective antimicrobial and anti-endotoxin activities. Sci. Rep. 7: 3384-3400spa
dcterms.referencesUteng, M., Hauge, H.H., Markwick, P.R., Fimland, G., Mantzilas, D., Nissen-Meyer, J., Muhle-Goll, C. (2003). Three-dimensional structure in lipid micelles of the pediocin-like antimicrobial peptide sakacin P and a sakacin P variant that is structurally stabilized by an in- serted C-terminal disulfide bridge. Biochemistry. 42: 11417- 11426spa
dcterms.referencesVermeer, L.S., Lan, Y., Abbate, V., Ruh, E., Bui, T.T., Wilkinson, L.J., Kanno, T., Jumagulova, E., Kozlowska, J., Patel, J., McIntre, C.A., Yam, W.C., Ciu, G., Atkinson, R.A., Lam, J.K., Bansal, S.S, Drake, A.F., Mitchell, G.H., Mason, A.J. (2012). Conformational flexibility determines selectivity and antibacterial, antiplasmodial, and anticancer potency of cationic-helical peptides. J. Biol. Chem. 287: 34120-34133spa
dcterms.referencesVila-Farrés, X., Giralt, E., Vila, J. (2012). Update of peptides with antibacterial activity, Curr. Med. Chem. 19: 6188-98spa
dcterms.referencesWorld Health Organization – WHO. (2017). La OMS publica la lista de las bacterias para las que se necesitan urgentemente nuevos antibióticos. Fecha de consulta: 23 de marzo de 2019. Disponible en: https://www.who.int/es/news-room/detail/27-02-2017-who-publishes-list-of-bacteria-for-which-new-antibiotics-are-urgently-neededspa
dcterms.referencesneededYang, N., Liu, X., Teng, D., Li, Z., Wang, X., Mao, R., Wang, X., Hao, Y., Wang, J. (2017). Antibacterial and detoxifying activity of NZ17074 analogues with multi-layers of selective antimicrobial actions against Escherichia coli and Salmonella enteritidis. Sci. Rep. 7: 3392-3411spa
dcterms.referencesYeaman, M. & Yount, N. (2003) Mechanisms of Antimicrobial Peptide Action and Resistance. Pharmacol. Rev. 55: 27-55spa
dcterms.referencesYoon, J. H., Ingale, S. L., Kim, J. S., Kim, K. H., Lee, S. H., Park, Y. K., Chae, B. J. (2014). Effects of dietary supplementation of synthetic antimicrobial peptide-A3 and P5 on growth performance, apparent total tract digestibility of nutrients, fecal and intestinal microflora and intestinal morphology in weanling pigs. Livestock Science. 159: 53-60.spa
dcterms.referencesYu, H., Wang, C., Feng, L., Cai, S., Liu, X., Qiao, X., Shi, N. Wang, H., Wang, Y. (2017). Cathelicidin-trypsin inhibitor loop conjugate represents a promising antibiotic candidate with protease stability. Sci. Rep. 7: 2600-2617spa
dcterms.referencesZhu, X., Dong, N., Wang, Z., Ma, Z., Zhang, L., Ma, Q., Shan, A. (2014). Design of imperfectly amphipathic α-helical antimicrobial peptides with enhanced cell selectivity. Acta Biomater. 10: 244-257spa
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