Avaliação do perfil de resistência cruzada em cepa de Klebsiella Pneumoniae resistente ao peptídeo PADBS1R1

Detalhes bibliográficos
Autor(a) principal: Costa, Mylena Cardoso da
Data de Publicação: 2020
Tipo de documento: Trabalho de conclusão de curso
Idioma: por
Título da fonte: Repositório do Centro Universitário Braz Cubas
Texto Completo: https://repositorio.cruzeirodosul.edu.br/handle/123456789/1527
Resumo: The multi-resistant bacteria emergence has become a public health worldwide concern, mainly Gram-negative bacteria. Among then, Klebsiella pneumoniae responsible for several cases of infections, including urinary tract infections, pneumonia, bacteremia and liver abscesses. In this scenario, new antimicrobial compounds development has become a necessity. Antimicrobial peptides are considered a potent alternative for diseases treatment due their broad antimicrobial activity and their versatile character that makes it possible to design new molecules. Nevertheless, bacterial resistance to peptides has started to be reported in recent years. The development of peptides resistance can decrease susceptibility to others antimicrobial agents such as antibiotics, a phenomenon known as cross-resistance. This study aimed to evaluate the cross-resistance profile of Klebsiella pneumoniae resistant to PaDBS1R1 peptide, in order to anticipate possible consequences for clinical application. Peptide resistance was induced through evolutionary trajectory, by which the bacteria was challenged to sub-inhibitory peptide concentrations. The challenged strain achieved a minimum inhibitory concentration (MIC) of 60.8 μM, a concentration four times higher than the MIC of the parental strain (15.2 μM). In order to assess the cross-resistance profile, MIC tests were performed by microdilution and disk diffusion with amikacin, polymyxin B, colistin, ertapenem, gentamicin, imipenem, ciprofloxacin, ceftriaxone, cefepime, meropenem, tetracycline and tigecycline. The parental strain was sensitive to all antibiotics tested, differently of the challenged strain which showed resistance to polymyxin B, colistin, ciprofloxacin, ceftriaxone, meropenem and tigecycline. Thus, a peptide-resistant strain developed cross-resistance to antibiotics, possibly through changes in membrane and porins along with an expression of efflux pumps, requiring further studies to elucidate the mechanisms of resistance.
id CUB_a88327211ff66cf885655f63064ff2f9
oai_identifier_str oai:repositorio.cruzeirodosul.edu.br:123456789/1527
network_acronym_str CUB
network_name_str Repositório do Centro Universitário Braz Cubas
repository_id_str
spelling Avaliação do perfil de resistência cruzada em cepa de Klebsiella Pneumoniae resistente ao peptídeo PADBS1R1Klebsiella pneumoniaePeptídeos antimicrobianosresistência cruzadaresistência9.06.00.00-2 BiomedicinaThe multi-resistant bacteria emergence has become a public health worldwide concern, mainly Gram-negative bacteria. Among then, Klebsiella pneumoniae responsible for several cases of infections, including urinary tract infections, pneumonia, bacteremia and liver abscesses. In this scenario, new antimicrobial compounds development has become a necessity. Antimicrobial peptides are considered a potent alternative for diseases treatment due their broad antimicrobial activity and their versatile character that makes it possible to design new molecules. Nevertheless, bacterial resistance to peptides has started to be reported in recent years. The development of peptides resistance can decrease susceptibility to others antimicrobial agents such as antibiotics, a phenomenon known as cross-resistance. This study aimed to evaluate the cross-resistance profile of Klebsiella pneumoniae resistant to PaDBS1R1 peptide, in order to anticipate possible consequences for clinical application. Peptide resistance was induced through evolutionary trajectory, by which the bacteria was challenged to sub-inhibitory peptide concentrations. The challenged strain achieved a minimum inhibitory concentration (MIC) of 60.8 μM, a concentration four times higher than the MIC of the parental strain (15.2 μM). In order to assess the cross-resistance profile, MIC tests were performed by microdilution and disk diffusion with amikacin, polymyxin B, colistin, ertapenem, gentamicin, imipenem, ciprofloxacin, ceftriaxone, cefepime, meropenem, tetracycline and tigecycline. The parental strain was sensitive to all antibiotics tested, differently of the challenged strain which showed resistance to polymyxin B, colistin, ciprofloxacin, ceftriaxone, meropenem and tigecycline. Thus, a peptide-resistant strain developed cross-resistance to antibiotics, possibly through changes in membrane and porins along with an expression of efflux pumps, requiring further studies to elucidate the mechanisms of resistance.Agência 1O surgimento de bactérias multirresistentes tornou-se uma preocupação de saúde pública em todo o mundo, principalmente em bactérias Gram-negativas. Dentre elas Klebsiella pneumoniae mostra-se responsável por diversos casos de infecções, incluindo infecções do trato urinário, pneumonia, bacteremia e abscessos hepáticos. Neste cenário, o desenvolvimento de novos compostos antimicrobianos se tornou uma necessidade. Os peptídeos antimicrobianos são considerados uma potente alternativa para o tratamento de infecções devido a sua PAMla atividade antimicrobiana e seu caráter versátil que possibilita o desenho de novas moléculas, porém a resistência bacteriana aos peptídeos começou a ser relatada nos últimos anos. O desenvolvimento da resistência a peptídeos pode diminuir a suscetibilidade a outros agentes antimicrobianos como antibióticos, fenômeno este conhecido como resistência cruzada. Este estudo teve objetivou avaliar o perfil de resistência cruzada de Klebsiella pneumoniae resistente ao peptídeo PaDBS1R1, a fim de antecipar possíveis consequências à aplicação clínica. A resistência ao peptídeo foi induzida através da trajetória evolutiva, pela qual a bactéria foi desafiada a variadas concentrações do peptídeo. A cepa desafiada apresentou concentração inibitória mínima (CIM) de 60.8 μM, concentração quatro vezes maior que a CIM da cepa parental (15.2 μM). A fim de avaliar o perfil de resistência cruzada foram realizados testes de CIM por microdiluição e testes de disco difusão com amicacina, polimixina B, colistina, ertapenem, gentamicina, imipenem, ciprofloxacino, ceftriaxona, cefepime, meropenem, tetraciclina e tigeciclina. A cepa parental apresentou sensibilidade a todos os antibióticos testados, diferentemente da cepa experimento que se demonstrou resistente a polimixina B, colistina, ciprofloxacino, ceftriaxona, meropenem e tigeciclina. Sendo assim, a cepa resistente ao peptídeo desenvolveu resistência cruzada aos antibióticos, possivelmente através de alterações na membrana e em porinas juntamente com a expressão de bomba de efluxo, sendo necessário estudos adicionais para elucidar os mecanismos de resistência.Instituto Brasileiro de Informação em Ciência e TecnologiaBrasilCoordenação do curso de BiomedicinaUDFGomes, Helder Andrey Rochahttp://lattes.cnpq.br/4972382847829089Franco, Octávio Luizhttp://lattes.cnpq.br/8598274096498065Costa, Mylena Cardoso da2021-02-12T19:00:35Z2021-02-122021-02-12T19:00:35Z2020info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/bachelorThesisapplication/pdfhttps://repositorio.cruzeirodosul.edu.br/handle/123456789/1527porABDI, M., MIRKALANTARI, S., & AMIRMOZAFARI, N. Bacterial resistance to antimicrobial peptides. Journal of Peptide Science, v.25, n.11, p.1-10, 2019. ADITI PRIYADARSHINI, B., MAHALAKSHMI, K., & NAVEEN KUMAR, V. Mutant Prevention Concentration of Ciprofloxacin against Klebsiella pneumoniae Clinical Isolates: An Ideal Prognosticator in Treating Multidrug-Resistant Strains. International Journal of Microbiology, v.2019, p.1-6, 2019. AL-FARSI, H. M., AL-ADWANI, S., AHMED, S., VOGT, C., AMBIKAN, A. T., LEBER, A., BERGMAN, P. Effects of the Antimicrobial Peptide LL-37 and Innate Effector Mechanisms in Colistin-Resistant Klebsiella pneumoniae With mgrB Insertions. Frontiers in Microbiology, v.10, p.1-11, 2019. ANDERSSON, D. I., HUGHES, D., & KUBICEK-SUTHERLAND, J. Z. Mechanisms and consequences of bacterial resistance to antimicrobial peptides. Drug Resistance Updates, v.26, p.43–57, 2016. ARZANLOU, M., CHAI, W. C., & VENTER, H. Intrinsic, adaptive and acquired antimicrobial resistance in Gram-negative bacteria. Essays In Biochemistry, v.61, n.1, p.49–59, 2017. BARBOSA, C., TREBOSC, V., KEMMER, C., ROSENSTIEL, P., BEARDMORE, R., SCHULENBURG, H., & JANSEN, G. Alternative Evolutionary Paths to Bacterial Antibiotic Resistance Cause Distinct Collateral Effects. Molecular Biology and Evolution, v.34, n.9, p.2229–2244, 2017. BECHINGER, B., & GORR, S.-U. Antimicrobial Peptides: Mechanisms of Action and Resistance. Journal of Dental Research, v.96, n.3, p.254–260, 2016. BERNARIDNI, A., CUESTA, T., TOMÁS, A., BENGOECHEA, J. A., MARTÍNEZ, J. L., & Sánchez SÁNCHEZ, M. B. The intrinsic resistome of Klebsiella pneumoniae. International Journal of Antimicrobial Agents, v.53, n.1, p.29-33, 2018. BLAIR B, J. M. A., WEBBER, M. A., BAYLAY, A. J., OGBOLU, D. O., & PIDDOCK, L. J. V. Molecular mechanisms of antibiotic resistance. Nature Reviews Microbiology, v.13, n.1, p.42–51, 2014. BHAGIRATH, A. Y., LI, Y., PATIDAR, R., YEREX, K., MA, X., KUMAR, A., & DUAN, K. Two Component Regulatory Systems and Antibiotic Resistance in Gram-Negative Pathogens. International Journal of Molecular Sciences, v.20, n.7, p.1781, 2019. CHEUNG, G. Y., & OTTO, M. Do antimicrobial peptides and antimicrobial-peptide resistance play important roles during bacterial infection? Future Microbiology, v.13, n.10, p.1073-1075, 2019. CHEW, K. L., LIN, R. T. P., & TEO, J. W. P. Klebsiella pneumoniae in Singapore: Hypervirulent Infections and the Carbapenemase Threat. Frontiers in Cellular and Infection Microbiology, v.7, p.1-8, 2017. CLSI. Me 1thods for Dilution Antimicrobial Susceptibility Tests for Bacteria That Grow Aerobically; Approved Standard-Tenth Edition. CLSI document M07-A10. Wayne, P: Clinical and a Laboratory Standards Institute, 2015. CLSI. Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria That Grow Aerobically; Approved Standard-Tenth Edition. CLSI document M02-A12. Wayne, P: Clinical and a Laboratory Standards Institute, 2015. CLSI. Performance Standards for Antimicrobial Susceptibility Testing. 28ª edição CLSI M100. Wayne, P.A: Clinical and Laboratory Standards Institute, 2018. COLCLOUGH, A., CORANDER, J., SHEPPARD, S., BAYLISS, S., & VOS, M. Patterns of cross-resistance and collateral sensitivity between clinical antibiotics and natural antimicrobials. Evolutionary Applications, v.12, n.5, p.878-887, 2019. DA COSTA, A. L. P., JUNIOR, A. C. S. S. Resistência bacteriana aos antibióticos e Saúde Pública: uma breve revisão de literatura. Estação Científica (UNIFAP), Macapá, v.7, n.2, p.45-57, 2019. DHILLON, S. Meropenem/Vaborbactam: A Review in Complicated Urinary Tract Infections. Drugs, v.78, n.12, p.1259-1270, 2018. DOORDUIJN, D. J., ROOIJAKKERS, S. H. M., VAN SCHAIK, W., & BARDOEL, B. W. Complement resistance mechanisms of Klebsiella pneumoniae. Immunobiology, v.221, n.10, p.1102–1109, 2016. DUVAL, R. E., GRARE, M., & DEMORÉ, B. Fight Against Antimicrobial Resistance: We Always Need New Antibacterials but for Right Bacteria. Molecules, v.24, n.17, p.3152, 2019. FISHER, J. F., & MOBASHERY, S. Constructing and Deconstructing the Bacterial Cell Wall. Protein Science, v.29, n.3, p.629-646, 2019. FOLLADOR, R., HEINZ, E., THOMSON, N. R., HOLT, K. E., KOWARIK, M., WYRES, K. L., & ELLINGTON, M. J. (2016). The diversity of Klebsiella pneumoniae surface polysaccharides. Microbial Genomics, v.2, n.8, p.1-15, 2019. FLEITAS, O., & FRANCO, O. L. Induced Bacterial Cross-Resistance toward Host Antimicrobial Peptides: A Worrying Phenomenon. Frontiers in Microbiology, n.7, p. 1-5, 2016. FLEITAS, O. M., DE SOUZA, C. M., DA COSTA, M. C., PORTO, W. F, SILVA, O. N., FRANCO, O. L. Understanding the Klebsiella pneumoniae resistance response to the antimicrobial peptide PaDBS1R1 from a proteomic perspective. Em fase de preparação, 2020. FRIEDLANDER C. Uber die scizomyceten bei der acuten fibrosen pneumonie. Archiv Für Pathologische Anatomie Und Physiologie Und Für Klinische Medicin, v.87, p.319 –324, 1882. FRIERI, M., KUMAR, K., & BOUTIN, A. Antibiotic resistance. Journal of Infection and Public Health, v.10, n.4, p.369–378, 2017. GAI, X.Y., BO, S.N., SHEN, N., ZHOU, Q.T., YIN, A.Y., & LU, W. Pharmacokinetic-pharmacodynamic analysis of ciprofloxacin in elderly Chinese patients with lower respiratory tract infections caused by Gram-negative bacteria. Chinese Medical Journal, v.132, n.6, p.638–646, 2019. HANEY, E. F., MANSOUR, S. C., & HANCOCK, R. E. W. Antimicrobial Peptides: An Introduction. Antimicrobial Peptides, p.3–22, 2016. HOOPER, D. C., & JACOBY, G. A. Topoisomerase Inhibitors: Fluoroquinolone Mechanisms of Action and Resistance. Cold Spring Harbor Perspectives in Medicine, v.6, n.9, p.1-21, 2016. HORINOUCHI, T., SUZUKI, S., KOTANI, H., TANABE, K., SAKATA, N., SHIMIZU, H., & FURUSAWA, C. Prediction of Cross-resistance and Collateral Sensitivity by Gene Expression profiles and Genomic Mutations. Scientific Reports, v.7, n.1, p.1-11, 2017. IRAZAZABAL, L. N., PORTO, W. F., FENSTERSEIFER, I. C. M., ALVES, E. S. F., MATOS, C. O., MENEZES, A. C. S., FRANCO, O. L. Fast and potent bactericidal membrane lytic activity of PaDBS1R1, a novel cationic antimicrobial peptide. Biochimica et Biophysica Acta (BBA) – Biomembranes, v.1861, n.1, p.178-190, 2018. JOO, H.-S., FU, C.-I., & OTTO, M. Bacterial strategies of resistance to antimicrobial peptides. Philosophical Transactions of the Royal Society B: Biological Sciences, v.371, n.1695, p.1-11, 2016. JORGENSEN, S. C. J., & RYBAK, M. J. Meropenem and Vaborbactam: Stepping up the Battle against Carbapenem-resistant Enterobacteriaceae. Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy, v.38, n.4, p.444–461, 2018. KABRA, R., CHAUHAN, N., KUMAR, A., INGALE, P., & SINGH, S. Efflux pumps and antimicrobial resistance: Paradoxical components in systems genomics. Progress in Biophysics and Molecular Biology, v.141, p.15-24, 2018. KIDD, T. J., MILLS, G., SÁ-PESSOA, J., DUMIGAN, A., FRANK, C. G., INSUA, J. L., BENGOECHEA, J. A. A Klebsiella pneumoniae antibiotic resistance mechanism that subdues host defences and promotes virulence.EMBO Molecular Medicine, v.9, n.4, p.430–447, 2017. KOULENTI, D., SONG, A., ELLINGBOE, A., ABDUL-AZIZ, M. H., HARRIS, P., GAVEY, E., & LIPMAN, J. Infections by multidrug-resistant Gram-negative Bacteria: what’s new in our arsenal and what’s in the pipeline? International Journal of Antimicrobial Agente, v.53, n.3, p.211-224, 2018. LAM, S. J., O’BRIEN-SIMPSON, N. M., PANTARAT, N., SULISTIO, A., WONG, E. H. H., CHEN, Y.-Y., QIAO, G. G. Combating multidrug-resistant Gram-negative bacteria with structurally nanoengineered antimicrobial peptide polymers. Nature Microbiology, v.1, n.11, p.1-11, 2016. LÁZÁR, V., MARTINS, A., SPOHN, R., DARUKA, L., GRÉZAL, G., FEKETE, G., PÁL, C. Antibiotic-resistant bacteria show widespread collateral sensitivity to antimicrobial peptides. Nature Microbiology, v.3, n.6, p.718–731, 2018. LÁZÁR, V., PAL SINGH, G., SPOHN, R., NAGY, I., HORVATH, B., HRTYAN, M., PAL, C. Bacterial evolution of antibiotic hypersensitivity. Molecular Systems Biology, v.9, n.1, p.700, 2014. LLOBET, E., MARTÍNEZ-MOLINER, V., MORANTA, D., DAHLSTRÖM, K. M., REGUEIRO, V., TOMÁS, A., BENGOECHEA, J. A. Deciphering tissue-induced Klebsiella pneumoniae lipid A structure. Proceedings of the National Academy of Sciences, v.112, n.46, p.6369–6378, 2015. LOFTON, H., PRÄNTING, M., THULIN, E., & ANDERSSON, D. I. Mechanisms and Fitness Costs of Resistance to Antimicrobial Peptides LL-37, CNY100HL and Wheat Germ Histones. PLoS ONE, v.8, n.7, p.1-13, 2013. MARTIN, R.M; BACHMAN, M.A. Colonization, Infection, and the Accessory Genome of Klebsiella pneumoniae. Frontiers in Cellular and Infection Microbiology, v.8, n.4, p.1-15, 2018. MIRANDA, I. F.; DOS SANTOS, M. L.; W. C. S. OLIVEIRA, W. C. S.; OLIVEIRA, M. C. Klebsiella pneumoniae Produtora de Carbapenemase do tipo KPC: disseminação mundial e situação atual no Brasil. Brazilian Journal of Surgery and Clinical Research, v.25, p.113–119, 2019. MOFFATT, JH, HARPER, M., & BOYCE, JD. Mecanismos de resistência à polimixina. Polymyxin Antibiotics: From Laboratory Bench to Bedside, v.1, p.55-71, 2019. MORAVEJ, H., MORAVEJ, Z., YAZDANPARAST, M., HEIAT, M., MIRHOSSEINI, A., MOOSAZADEH MOGHADDAM, M., & MIRNEJAD, R. Antimicrobial Peptides: Features, Action, and Their Resistance Mechanisms in Bacteria. Microbial Drug Resistance, v.24, n.6, p.747–767, 2018. MUNITA, J. M., & ARIAS, C. A. Mechanisms of Antibiotic Resistance. Virulence Mechanisms of Bacterial Pathogens, Fifth Edition, v.4, n.2, p.481–511, 2017. NAVON-VENEZIA, S., KONFRATYEVA, K., & CARATTOLI, A. Klebsiella pneumoniae: a major worldwide source and shuttle for antibiotic resistance. FEMS Microbiology Reviews, v.41, n.3, p.252–275, 2017. NOWICKI, E. M., O’BRIEN, J. P., BRODBELT, J. S., & TRENT, M. S. Extracellular zinc induces phosphoethanolamine addition to Pseudomonas aeruginosa lipid A via the ColRS two-component system. Molecular Microbiology, v.97, n.1, p.166–178, 2015. O’NEILL, J. Tackling drug-resistant infections globally: final report and recommendations. Review on Antimicrobial Resistance, v.82, p.1-84, 2016. PACZOSA, M. K., & MECSAS, J. Klebsiella pneumoniae: Going on the Offense with a Strong Defense. Microbiology and Molecular Biology Reviews, v.80, n.3, p. 629–661, 2016. PÁL, C., PAPP, B., & LÁZÁR, V. Collateral sensitivity of antibiotic-resistant microbes. Trends in Microbiology, v.23, n.7, p.401–407, 2015. PETERSON, E., & KAUR, P. Antibiotic Resistance Mechanisms in Bacteria: Relationships Between Resistance Determinants of Antibiotic Producers, Environmental Bacteria, and Clinical Pathogens. Frontiers in Microbiology, v.9, p. 1-21, 2018. PONTES, D. S., DE ARAUJO, R. S. A., DANTAS, N., SCOTTI, L., SCOTTI, M. T., DE MOURA, R. O., & MENDONCA- JUNIOR, F. J. B. Genetic Mechanisms of Antibiotic Resistance and the Role of Antibiotic Adjuvants. Current Topics in Medicinal Chemistry, v.18, n.1, p.42–74, 2018. PRAJAPATI, J. D., FERNÁNDEZ SOLANO, C. J., WINTERHALTER, M., & KLEINEKATÖFER, U. Characterization of Ciprofloxacin Permeation Pathways across the Porin OmpC Using Metadynamics and a String Method. Journal of Chemical Theory and Computation, v.13, n.9, p.4553–4566, 2017. SANTAJIT, S., & INDRAWATTANA, N. Mechanisms of Antimicrobial Resistance in ESKAPE Pathogens. BioMed Research International, v. 2016, p.1–8, 2016. SIERRA, J. M., FUSTÉ, E., RABANAL, F., VINUESA, T., & VINÃS, M. An overview of antimicrobial peptides and the latest advances in their development. Expert Opinion on Biological Therapy, v.17, n.6, p.663–676, 2017. SPOHN, R., DAKURA, L., LÁZÁR, V., MARTINS, A., VIDOVICS, F., GRÉZAL, G., PÁL, C. Integrated evolutionary analysis reveals antimicrobial peptides with limited resistance. Nature Communications, v.10, n.1, p.4538, 2019. SZYBALSKI W, BRYSON V. Genetic studies on microbial cross resistance to toxic agents, J. Bacteriol, v.64, p.489–499, 1952. THEURETZBACHER, U. Antibiotic innovation for future public health needs. Clinical Microbiology and Infection, v.23, n.10, p.713–717, 2017. TRIMBLE, M. J., MLYÁRCIK, P., KOLÁR, M., & HANCOCK, R. E. W. Polymyxin: Alternative Mechanisms of Action and Resistance. Cold Spring Harbor Perspectives in Medicine, v.6, n.10, p.1-22, 2016. UNEMO, M., GOLPARIAN, D., & EYRE, D. W. Antimicrobial Resistance in Neisseria gonorrhoeae and Treatment of Gonorrhea. Methods in Molecular Biology, v.2017, p.37–58, 2019. VOULGARIS, G. L., VOULGARI, M. L., & FALAGAS, M. E. Developments on antibiotics for multidrug resistant bacterial Gram-negative infections. Expert Review of Anti-Infective Therapy, v. 17, n.6, p.387-401, 2019. YOON, E.-J., OH, Y., & JEONG, S. H. Development of Tigecycline Resistance in Carbapenemase-Producing Klebsiella pneumoniae Sequence Type 147 via AcrAB Overproduction Mediated by Replacement of the ramA Promoter. Annals of Laboratory Medicine, v.40, n.1, p.15, 2020. ZHANEL, G. G., WIEBE, R., DILAY, L., THOMSON, K., RUBINSTEIN, E., HOBAN, D. J., KARLOWSKY, J. A. Comparative Review of the Carbapenems. Drugs, v.67, n.7, p.1027–1052, 2007.info:eu-repo/semantics/openAccessreponame:Repositório do Centro Universitário Braz Cubasinstname:Centro Universitário Braz Cubas (CUB)instacron:CUB2021-02-12T19:03:02Zoai:repositorio.cruzeirodosul.edu.br:123456789/1527Repositório InstitucionalPUBhttps://repositorio.brazcubas.edu.br/oai/requestbibli@brazcubas.edu.bropendoar:2021-02-12T19:03:02Repositório do Centro Universitário Braz Cubas - Centro Universitário Braz Cubas (CUB)false
dc.title.none.fl_str_mv Avaliação do perfil de resistência cruzada em cepa de Klebsiella Pneumoniae resistente ao peptídeo PADBS1R1
title Avaliação do perfil de resistência cruzada em cepa de Klebsiella Pneumoniae resistente ao peptídeo PADBS1R1
spellingShingle Avaliação do perfil de resistência cruzada em cepa de Klebsiella Pneumoniae resistente ao peptídeo PADBS1R1
Costa, Mylena Cardoso da
Klebsiella pneumoniae
Peptídeos antimicrobianos
resistência cruzada
resistência
9.06.00.00-2 Biomedicina
title_short Avaliação do perfil de resistência cruzada em cepa de Klebsiella Pneumoniae resistente ao peptídeo PADBS1R1
title_full Avaliação do perfil de resistência cruzada em cepa de Klebsiella Pneumoniae resistente ao peptídeo PADBS1R1
title_fullStr Avaliação do perfil de resistência cruzada em cepa de Klebsiella Pneumoniae resistente ao peptídeo PADBS1R1
title_full_unstemmed Avaliação do perfil de resistência cruzada em cepa de Klebsiella Pneumoniae resistente ao peptídeo PADBS1R1
title_sort Avaliação do perfil de resistência cruzada em cepa de Klebsiella Pneumoniae resistente ao peptídeo PADBS1R1
author Costa, Mylena Cardoso da
author_facet Costa, Mylena Cardoso da
author_role author
dc.contributor.none.fl_str_mv Gomes, Helder Andrey Rocha
http://lattes.cnpq.br/4972382847829089
Franco, Octávio Luiz
http://lattes.cnpq.br/8598274096498065
dc.contributor.author.fl_str_mv Costa, Mylena Cardoso da
dc.subject.por.fl_str_mv Klebsiella pneumoniae
Peptídeos antimicrobianos
resistência cruzada
resistência
9.06.00.00-2 Biomedicina
topic Klebsiella pneumoniae
Peptídeos antimicrobianos
resistência cruzada
resistência
9.06.00.00-2 Biomedicina
description The multi-resistant bacteria emergence has become a public health worldwide concern, mainly Gram-negative bacteria. Among then, Klebsiella pneumoniae responsible for several cases of infections, including urinary tract infections, pneumonia, bacteremia and liver abscesses. In this scenario, new antimicrobial compounds development has become a necessity. Antimicrobial peptides are considered a potent alternative for diseases treatment due their broad antimicrobial activity and their versatile character that makes it possible to design new molecules. Nevertheless, bacterial resistance to peptides has started to be reported in recent years. The development of peptides resistance can decrease susceptibility to others antimicrobial agents such as antibiotics, a phenomenon known as cross-resistance. This study aimed to evaluate the cross-resistance profile of Klebsiella pneumoniae resistant to PaDBS1R1 peptide, in order to anticipate possible consequences for clinical application. Peptide resistance was induced through evolutionary trajectory, by which the bacteria was challenged to sub-inhibitory peptide concentrations. The challenged strain achieved a minimum inhibitory concentration (MIC) of 60.8 μM, a concentration four times higher than the MIC of the parental strain (15.2 μM). In order to assess the cross-resistance profile, MIC tests were performed by microdilution and disk diffusion with amikacin, polymyxin B, colistin, ertapenem, gentamicin, imipenem, ciprofloxacin, ceftriaxone, cefepime, meropenem, tetracycline and tigecycline. The parental strain was sensitive to all antibiotics tested, differently of the challenged strain which showed resistance to polymyxin B, colistin, ciprofloxacin, ceftriaxone, meropenem and tigecycline. Thus, a peptide-resistant strain developed cross-resistance to antibiotics, possibly through changes in membrane and porins along with an expression of efflux pumps, requiring further studies to elucidate the mechanisms of resistance.
publishDate 2020
dc.date.none.fl_str_mv 2020
2021-02-12T19:00:35Z
2021-02-12
2021-02-12T19:00:35Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/bachelorThesis
format bachelorThesis
status_str publishedVersion
dc.identifier.uri.fl_str_mv https://repositorio.cruzeirodosul.edu.br/handle/123456789/1527
url https://repositorio.cruzeirodosul.edu.br/handle/123456789/1527
dc.language.iso.fl_str_mv por
language por
dc.relation.none.fl_str_mv ABDI, M., MIRKALANTARI, S., & AMIRMOZAFARI, N. Bacterial resistance to antimicrobial peptides. Journal of Peptide Science, v.25, n.11, p.1-10, 2019. ADITI PRIYADARSHINI, B., MAHALAKSHMI, K., & NAVEEN KUMAR, V. Mutant Prevention Concentration of Ciprofloxacin against Klebsiella pneumoniae Clinical Isolates: An Ideal Prognosticator in Treating Multidrug-Resistant Strains. International Journal of Microbiology, v.2019, p.1-6, 2019. AL-FARSI, H. M., AL-ADWANI, S., AHMED, S., VOGT, C., AMBIKAN, A. T., LEBER, A., BERGMAN, P. Effects of the Antimicrobial Peptide LL-37 and Innate Effector Mechanisms in Colistin-Resistant Klebsiella pneumoniae With mgrB Insertions. Frontiers in Microbiology, v.10, p.1-11, 2019. ANDERSSON, D. I., HUGHES, D., & KUBICEK-SUTHERLAND, J. Z. Mechanisms and consequences of bacterial resistance to antimicrobial peptides. Drug Resistance Updates, v.26, p.43–57, 2016. ARZANLOU, M., CHAI, W. C., & VENTER, H. Intrinsic, adaptive and acquired antimicrobial resistance in Gram-negative bacteria. Essays In Biochemistry, v.61, n.1, p.49–59, 2017. BARBOSA, C., TREBOSC, V., KEMMER, C., ROSENSTIEL, P., BEARDMORE, R., SCHULENBURG, H., & JANSEN, G. Alternative Evolutionary Paths to Bacterial Antibiotic Resistance Cause Distinct Collateral Effects. Molecular Biology and Evolution, v.34, n.9, p.2229–2244, 2017. BECHINGER, B., & GORR, S.-U. Antimicrobial Peptides: Mechanisms of Action and Resistance. Journal of Dental Research, v.96, n.3, p.254–260, 2016. BERNARIDNI, A., CUESTA, T., TOMÁS, A., BENGOECHEA, J. A., MARTÍNEZ, J. L., & Sánchez SÁNCHEZ, M. B. The intrinsic resistome of Klebsiella pneumoniae. International Journal of Antimicrobial Agents, v.53, n.1, p.29-33, 2018. BLAIR B, J. M. A., WEBBER, M. A., BAYLAY, A. J., OGBOLU, D. O., & PIDDOCK, L. J. V. Molecular mechanisms of antibiotic resistance. Nature Reviews Microbiology, v.13, n.1, p.42–51, 2014. BHAGIRATH, A. Y., LI, Y., PATIDAR, R., YEREX, K., MA, X., KUMAR, A., & DUAN, K. Two Component Regulatory Systems and Antibiotic Resistance in Gram-Negative Pathogens. International Journal of Molecular Sciences, v.20, n.7, p.1781, 2019. CHEUNG, G. Y., & OTTO, M. Do antimicrobial peptides and antimicrobial-peptide resistance play important roles during bacterial infection? Future Microbiology, v.13, n.10, p.1073-1075, 2019. CHEW, K. L., LIN, R. T. P., & TEO, J. W. P. Klebsiella pneumoniae in Singapore: Hypervirulent Infections and the Carbapenemase Threat. Frontiers in Cellular and Infection Microbiology, v.7, p.1-8, 2017. CLSI. Me 1thods for Dilution Antimicrobial Susceptibility Tests for Bacteria That Grow Aerobically; Approved Standard-Tenth Edition. CLSI document M07-A10. Wayne, P: Clinical and a Laboratory Standards Institute, 2015. CLSI. Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria That Grow Aerobically; Approved Standard-Tenth Edition. CLSI document M02-A12. Wayne, P: Clinical and a Laboratory Standards Institute, 2015. CLSI. Performance Standards for Antimicrobial Susceptibility Testing. 28ª edição CLSI M100. Wayne, P.A: Clinical and Laboratory Standards Institute, 2018. COLCLOUGH, A., CORANDER, J., SHEPPARD, S., BAYLISS, S., & VOS, M. Patterns of cross-resistance and collateral sensitivity between clinical antibiotics and natural antimicrobials. Evolutionary Applications, v.12, n.5, p.878-887, 2019. DA COSTA, A. L. P., JUNIOR, A. C. S. S. Resistência bacteriana aos antibióticos e Saúde Pública: uma breve revisão de literatura. Estação Científica (UNIFAP), Macapá, v.7, n.2, p.45-57, 2019. DHILLON, S. Meropenem/Vaborbactam: A Review in Complicated Urinary Tract Infections. Drugs, v.78, n.12, p.1259-1270, 2018. DOORDUIJN, D. J., ROOIJAKKERS, S. H. M., VAN SCHAIK, W., & BARDOEL, B. W. Complement resistance mechanisms of Klebsiella pneumoniae. Immunobiology, v.221, n.10, p.1102–1109, 2016. DUVAL, R. E., GRARE, M., & DEMORÉ, B. Fight Against Antimicrobial Resistance: We Always Need New Antibacterials but for Right Bacteria. Molecules, v.24, n.17, p.3152, 2019. FISHER, J. F., & MOBASHERY, S. Constructing and Deconstructing the Bacterial Cell Wall. Protein Science, v.29, n.3, p.629-646, 2019. FOLLADOR, R., HEINZ, E., THOMSON, N. R., HOLT, K. E., KOWARIK, M., WYRES, K. L., & ELLINGTON, M. J. (2016). The diversity of Klebsiella pneumoniae surface polysaccharides. Microbial Genomics, v.2, n.8, p.1-15, 2019. FLEITAS, O., & FRANCO, O. L. Induced Bacterial Cross-Resistance toward Host Antimicrobial Peptides: A Worrying Phenomenon. Frontiers in Microbiology, n.7, p. 1-5, 2016. FLEITAS, O. M., DE SOUZA, C. M., DA COSTA, M. C., PORTO, W. F, SILVA, O. N., FRANCO, O. L. Understanding the Klebsiella pneumoniae resistance response to the antimicrobial peptide PaDBS1R1 from a proteomic perspective. Em fase de preparação, 2020. FRIEDLANDER C. Uber die scizomyceten bei der acuten fibrosen pneumonie. Archiv Für Pathologische Anatomie Und Physiologie Und Für Klinische Medicin, v.87, p.319 –324, 1882. FRIERI, M., KUMAR, K., & BOUTIN, A. Antibiotic resistance. Journal of Infection and Public Health, v.10, n.4, p.369–378, 2017. GAI, X.Y., BO, S.N., SHEN, N., ZHOU, Q.T., YIN, A.Y., & LU, W. Pharmacokinetic-pharmacodynamic analysis of ciprofloxacin in elderly Chinese patients with lower respiratory tract infections caused by Gram-negative bacteria. Chinese Medical Journal, v.132, n.6, p.638–646, 2019. HANEY, E. F., MANSOUR, S. C., & HANCOCK, R. E. W. Antimicrobial Peptides: An Introduction. Antimicrobial Peptides, p.3–22, 2016. HOOPER, D. C., & JACOBY, G. A. Topoisomerase Inhibitors: Fluoroquinolone Mechanisms of Action and Resistance. Cold Spring Harbor Perspectives in Medicine, v.6, n.9, p.1-21, 2016. HORINOUCHI, T., SUZUKI, S., KOTANI, H., TANABE, K., SAKATA, N., SHIMIZU, H., & FURUSAWA, C. Prediction of Cross-resistance and Collateral Sensitivity by Gene Expression profiles and Genomic Mutations. Scientific Reports, v.7, n.1, p.1-11, 2017. IRAZAZABAL, L. N., PORTO, W. F., FENSTERSEIFER, I. C. M., ALVES, E. S. F., MATOS, C. O., MENEZES, A. C. S., FRANCO, O. L. Fast and potent bactericidal membrane lytic activity of PaDBS1R1, a novel cationic antimicrobial peptide. Biochimica et Biophysica Acta (BBA) – Biomembranes, v.1861, n.1, p.178-190, 2018. JOO, H.-S., FU, C.-I., & OTTO, M. Bacterial strategies of resistance to antimicrobial peptides. Philosophical Transactions of the Royal Society B: Biological Sciences, v.371, n.1695, p.1-11, 2016. JORGENSEN, S. C. J., & RYBAK, M. J. Meropenem and Vaborbactam: Stepping up the Battle against Carbapenem-resistant Enterobacteriaceae. Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy, v.38, n.4, p.444–461, 2018. KABRA, R., CHAUHAN, N., KUMAR, A., INGALE, P., & SINGH, S. Efflux pumps and antimicrobial resistance: Paradoxical components in systems genomics. Progress in Biophysics and Molecular Biology, v.141, p.15-24, 2018. KIDD, T. J., MILLS, G., SÁ-PESSOA, J., DUMIGAN, A., FRANK, C. G., INSUA, J. L., BENGOECHEA, J. A. A Klebsiella pneumoniae antibiotic resistance mechanism that subdues host defences and promotes virulence.EMBO Molecular Medicine, v.9, n.4, p.430–447, 2017. KOULENTI, D., SONG, A., ELLINGBOE, A., ABDUL-AZIZ, M. H., HARRIS, P., GAVEY, E., & LIPMAN, J. Infections by multidrug-resistant Gram-negative Bacteria: what’s new in our arsenal and what’s in the pipeline? International Journal of Antimicrobial Agente, v.53, n.3, p.211-224, 2018. LAM, S. J., O’BRIEN-SIMPSON, N. M., PANTARAT, N., SULISTIO, A., WONG, E. H. H., CHEN, Y.-Y., QIAO, G. G. Combating multidrug-resistant Gram-negative bacteria with structurally nanoengineered antimicrobial peptide polymers. Nature Microbiology, v.1, n.11, p.1-11, 2016. LÁZÁR, V., MARTINS, A., SPOHN, R., DARUKA, L., GRÉZAL, G., FEKETE, G., PÁL, C. Antibiotic-resistant bacteria show widespread collateral sensitivity to antimicrobial peptides. Nature Microbiology, v.3, n.6, p.718–731, 2018. LÁZÁR, V., PAL SINGH, G., SPOHN, R., NAGY, I., HORVATH, B., HRTYAN, M., PAL, C. Bacterial evolution of antibiotic hypersensitivity. Molecular Systems Biology, v.9, n.1, p.700, 2014. LLOBET, E., MARTÍNEZ-MOLINER, V., MORANTA, D., DAHLSTRÖM, K. M., REGUEIRO, V., TOMÁS, A., BENGOECHEA, J. A. Deciphering tissue-induced Klebsiella pneumoniae lipid A structure. Proceedings of the National Academy of Sciences, v.112, n.46, p.6369–6378, 2015. LOFTON, H., PRÄNTING, M., THULIN, E., & ANDERSSON, D. I. Mechanisms and Fitness Costs of Resistance to Antimicrobial Peptides LL-37, CNY100HL and Wheat Germ Histones. PLoS ONE, v.8, n.7, p.1-13, 2013. MARTIN, R.M; BACHMAN, M.A. Colonization, Infection, and the Accessory Genome of Klebsiella pneumoniae. Frontiers in Cellular and Infection Microbiology, v.8, n.4, p.1-15, 2018. MIRANDA, I. F.; DOS SANTOS, M. L.; W. C. S. OLIVEIRA, W. C. S.; OLIVEIRA, M. C. Klebsiella pneumoniae Produtora de Carbapenemase do tipo KPC: disseminação mundial e situação atual no Brasil. Brazilian Journal of Surgery and Clinical Research, v.25, p.113–119, 2019. MOFFATT, JH, HARPER, M., & BOYCE, JD. Mecanismos de resistência à polimixina. Polymyxin Antibiotics: From Laboratory Bench to Bedside, v.1, p.55-71, 2019. MORAVEJ, H., MORAVEJ, Z., YAZDANPARAST, M., HEIAT, M., MIRHOSSEINI, A., MOOSAZADEH MOGHADDAM, M., & MIRNEJAD, R. Antimicrobial Peptides: Features, Action, and Their Resistance Mechanisms in Bacteria. Microbial Drug Resistance, v.24, n.6, p.747–767, 2018. MUNITA, J. M., & ARIAS, C. A. Mechanisms of Antibiotic Resistance. Virulence Mechanisms of Bacterial Pathogens, Fifth Edition, v.4, n.2, p.481–511, 2017. NAVON-VENEZIA, S., KONFRATYEVA, K., & CARATTOLI, A. Klebsiella pneumoniae: a major worldwide source and shuttle for antibiotic resistance. FEMS Microbiology Reviews, v.41, n.3, p.252–275, 2017. NOWICKI, E. M., O’BRIEN, J. P., BRODBELT, J. S., & TRENT, M. S. Extracellular zinc induces phosphoethanolamine addition to Pseudomonas aeruginosa lipid A via the ColRS two-component system. Molecular Microbiology, v.97, n.1, p.166–178, 2015. O’NEILL, J. Tackling drug-resistant infections globally: final report and recommendations. Review on Antimicrobial Resistance, v.82, p.1-84, 2016. PACZOSA, M. K., & MECSAS, J. Klebsiella pneumoniae: Going on the Offense with a Strong Defense. Microbiology and Molecular Biology Reviews, v.80, n.3, p. 629–661, 2016. PÁL, C., PAPP, B., & LÁZÁR, V. Collateral sensitivity of antibiotic-resistant microbes. Trends in Microbiology, v.23, n.7, p.401–407, 2015. PETERSON, E., & KAUR, P. Antibiotic Resistance Mechanisms in Bacteria: Relationships Between Resistance Determinants of Antibiotic Producers, Environmental Bacteria, and Clinical Pathogens. Frontiers in Microbiology, v.9, p. 1-21, 2018. PONTES, D. S., DE ARAUJO, R. S. A., DANTAS, N., SCOTTI, L., SCOTTI, M. T., DE MOURA, R. O., & MENDONCA- JUNIOR, F. J. B. Genetic Mechanisms of Antibiotic Resistance and the Role of Antibiotic Adjuvants. Current Topics in Medicinal Chemistry, v.18, n.1, p.42–74, 2018. PRAJAPATI, J. D., FERNÁNDEZ SOLANO, C. J., WINTERHALTER, M., & KLEINEKATÖFER, U. Characterization of Ciprofloxacin Permeation Pathways across the Porin OmpC Using Metadynamics and a String Method. Journal of Chemical Theory and Computation, v.13, n.9, p.4553–4566, 2017. SANTAJIT, S., & INDRAWATTANA, N. Mechanisms of Antimicrobial Resistance in ESKAPE Pathogens. BioMed Research International, v. 2016, p.1–8, 2016. SIERRA, J. M., FUSTÉ, E., RABANAL, F., VINUESA, T., & VINÃS, M. An overview of antimicrobial peptides and the latest advances in their development. Expert Opinion on Biological Therapy, v.17, n.6, p.663–676, 2017. SPOHN, R., DAKURA, L., LÁZÁR, V., MARTINS, A., VIDOVICS, F., GRÉZAL, G., PÁL, C. Integrated evolutionary analysis reveals antimicrobial peptides with limited resistance. Nature Communications, v.10, n.1, p.4538, 2019. SZYBALSKI W, BRYSON V. Genetic studies on microbial cross resistance to toxic agents, J. Bacteriol, v.64, p.489–499, 1952. THEURETZBACHER, U. Antibiotic innovation for future public health needs. Clinical Microbiology and Infection, v.23, n.10, p.713–717, 2017. TRIMBLE, M. J., MLYÁRCIK, P., KOLÁR, M., & HANCOCK, R. E. W. Polymyxin: Alternative Mechanisms of Action and Resistance. Cold Spring Harbor Perspectives in Medicine, v.6, n.10, p.1-22, 2016. UNEMO, M., GOLPARIAN, D., & EYRE, D. W. Antimicrobial Resistance in Neisseria gonorrhoeae and Treatment of Gonorrhea. Methods in Molecular Biology, v.2017, p.37–58, 2019. VOULGARIS, G. L., VOULGARI, M. L., & FALAGAS, M. E. Developments on antibiotics for multidrug resistant bacterial Gram-negative infections. Expert Review of Anti-Infective Therapy, v. 17, n.6, p.387-401, 2019. YOON, E.-J., OH, Y., & JEONG, S. H. Development of Tigecycline Resistance in Carbapenemase-Producing Klebsiella pneumoniae Sequence Type 147 via AcrAB Overproduction Mediated by Replacement of the ramA Promoter. Annals of Laboratory Medicine, v.40, n.1, p.15, 2020. ZHANEL, G. G., WIEBE, R., DILAY, L., THOMSON, K., RUBINSTEIN, E., HOBAN, D. J., KARLOWSKY, J. A. Comparative Review of the Carbapenems. Drugs, v.67, n.7, p.1027–1052, 2007.
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Instituto Brasileiro de Informação em Ciência e Tecnologia
Brasil
Coordenação do curso de Biomedicina
UDF
publisher.none.fl_str_mv Instituto Brasileiro de Informação em Ciência e Tecnologia
Brasil
Coordenação do curso de Biomedicina
UDF
dc.source.none.fl_str_mv reponame:Repositório do Centro Universitário Braz Cubas
instname:Centro Universitário Braz Cubas (CUB)
instacron:CUB
instname_str Centro Universitário Braz Cubas (CUB)
instacron_str CUB
institution CUB
reponame_str Repositório do Centro Universitário Braz Cubas
collection Repositório do Centro Universitário Braz Cubas
repository.name.fl_str_mv Repositório do Centro Universitário Braz Cubas - Centro Universitário Braz Cubas (CUB)
repository.mail.fl_str_mv bibli@brazcubas.edu.br
_version_ 1798311353859964928

Registros relacionados