Study of the beta-lactamase enzyme and its relationship with antibiotic resistance

Authors

DOI:

https://doi.org/10.33448/rsd-v9i7.4594

Keywords:

Beta-lactamases; Drug resistance microbial; Computational biology.

Abstract

Beta-lactam antibiotics have the same mechanism of action, the inhibition of bacterial cell wall synthesis, mainly affecting peptidoglycan. They are considered safety antibiotics, since, when they directly reach the cell wall, they cause bacterial autolysis. The objective of this research is to evaluate the affinity between the beta-lactamase enzyme and several classes of beta-lactam antibiotics. This study is a research of exploratory type methodology, of quantitative nature with application of computer simulation with application of methods with computer simulation with the evaluation of the connection scores by traditional molecular anchoring using the AutoDock 4.2 program. We identified that, in the results of molecular docking simulations, penicillin and cephalosporin showed greater affinity at the catalytic site, due to a lower Gibbs free energy. It is concluded that the affinity of the antibiotics penicillin and cephalosporin may in the future represent an obstacle for the treatment of diseases such as, mild and moderate infections of the respiratory tract, skin infections, venereal infections, and the prophylaxis of rheumatic diseases. We suggest that further studies evaluate the simulations with molecular dynamics tests to see if, considering the flexibility of the enzyme, even more accurate results would be possible.

Author Biographies

Lorenna de Lourdes Costa Araújo, Centro Universitário Santo Agostinho

Graduanda em Enfermagem pelo Centro Universitário Santo Agostinho-UNIFSA

Francisco Honeidy Carvalho Azevedo, Centro Universitário Santo Agostinho

Doutor em Biologia Celular e Molecular pela Universidade Luterana do Brasil-RS – ULBRA-RS, Docente do Centro Universitário Santo Agostinho-UNIFSA

References

George, EA, Sankar, S, Jesudasan, MV, Sudandiradoss, C & Nandagopal, B. (2015). Molecular characterization of CTX-M type Extended Spectrum Beta Lactamase producing E. coli isolated from humans and the environment. Indian J Med Microbiol, 33,73–79.

Lima, DS, Lima, JC, Calvacanti, RMCB, Santos, BHC & Lima, IO. (2017). Estudo da atividade antibacteriana dos monoterpenos timol e carvacrol contra cepas de Escherichia coli produtoras de β-lactamases de amplo espectro. Ver Pan-Amaz Saúde, 8(1),17-21.

Sousa, ATHI, Makino, H, Bruno, VCM, Candido, SL, Nogueira, BS, Menezes, IG, Nakazato, L & Dutra, V. (2019). Perfil de resistência antimicrobiana de Klebsiella pneumoniae isoladas de animais domésticos e silvestres. Arquivo Brasileiro de Medicina Veterinária e Zootecnia, 71(2), 584-593.

Lteif, L & Eiland, LS. (2019). The Basics of Penicillin Allergy: What A Clinician Should Know. Pharmacy (Basel),7(3),94.

Choi, JH. (2019). Does Cephalosporin Skin Test Predict Immediate Hypersensitivity to Cephalosporin? J Korean Med Sci, 34(50).

Lee, Y & Bradley, N. (2019). Overview and Insights into Carbapenem Allergy. Pharmacy (Basel), 7(3).

Bush, K & Bradford, PA. (2016). β-Lactams and β-Lactamase Inhibitors: An Overview. Cold Spring Harb Perspect Med, 6(8), 025247.

Morehead, MS & Scarbrough, C. (2018). Emergence of Global Antibiotic Resistance. Prim Care, 45(3), 467–484.

Pdb - Protein Data Bank. (1999). rcsb.org. Acesso em: 10 abril 2020. Disponível em: http://www.rcsb.org/pages/about-us/index

Pereira, AS, Shitsuka, DM, Parreira, FJ & Shitsuka, R. (2018). Metodologia da pesquisa científica. [e-book]. Santa Maria. Ed. UAB/NTE/UFSM. Disponível em: https://repositorio.ufsm.br/bitstream/handle/1/15824/Lic_Computacao_Metodologia-Pesquisa-Cientifica.pdf?sequence=1.

Rose, PW, Ell, DS, Hudson, B, Kalro, T, Lowe, R, Peisach, E, Randle, C, Rose, AS, Shao, C, Tao, YP, Valasatava, Y, Voigt, M, Westbrook, JD, Woo, J, Yang, H, Young, JY, Zardecki, C, Berman, HM & Burley, SK. (2017). The RCSB protein data bank: Integrative view of protein, gene and 3D structural information. Nucleic Acids Res, 45, 271–281.

Jiankun, L, Sheng, W, Trent, EB, Isha, S, Anat, L, Yurii, SM, Matthew, JO’M, Tao, C, Enkhjargal, A, Kateryna, T, Andrey, AT, Brian, KS, Bryan, LR & John, JI. (2019). Ultra-large library docking for discovering new chemotypes. Nature, 566(7743), 224–229.

Foster, ME & Sohlberg, KA. (2010). New Empirical Correction to the AM1 Method for Macromolecular Complexes. J Chem Theory Comput, 6(7), 2153-66.

Acd /chemsketch para uso acadêmico e pessoal. (1996). acdlabs.com. Acesso em: 10 abril 2020. Disponível em: http://www.acdlabs.com/resources/freeware/chemsketch/

Soluções e serviços de software para química e biologia. (2020). Chemaxon.com. Acesso em: 10 abril 2020. Disponível em: https://www.chemaxon.com

Arguslab. (2020). Arguslab.com. Acesso em: 10 de abril de 2020. Disponível em: http://www.arguslab.com

Gasteiger, J & Marsili, M. (1980). Iterative partial equalization of orbital electronegativity- a rapid access to atomic charges. Tetrahedron, 36(22), 3219–3228.

Morris, GM, Huey, R, Lindstrom, W, Sanner, MF, Belew, RK, Goodsell, DS & Olson, AJ. (2009). AutoDock4 and AutoDockTools4: Automated docking with selective receptor flexibility. J. Comput, 30, 2785–2791.

Sanner, MF. (1999). Python: a programming language for software integration and development. J. Mol. Graph. Model, 17, 57–61.

Morris, GM, Goodsell, DS, Halliday, RS, Huey, R, Hart, WE, Belew, RK & Olson, AJ. (1998). Automated docking using a Lamarckian genetic algorithm and an empirical binding free energy function. J. Comput. Chem, 19, 1639–1662.

Solis, FJ, Wets, RJB. (1981). Minimization by Random Search Techniques. Math.Oper. Res, 6, 19–30.

Vergara, RC, Jaramillo-Riveri, S, Luarte, A, Moenne-loccoz, C, Fuentes, R, Couve, A & Maldonado, PE. (2019). The Energy Homeostasis Principle: Neuronal Energy Regulation Drives Local Network Dynamics Generating Behavior. Front Comput Neurosci,13,49.

Rietman, EA, Taylor, S, Siegelmann, HT, Deriu, MA, Cavaglia, M & Tuszynski, JA. (2020). Using the Gibbs Function as a Measure of Human Brain Development Trends from Fetal Stage to Advanced Age. Int J Mol Sci, 21(3),1116.

Ding, X, Vilseck, JZ, Hayes, RL & Brooks, CL. (2017). Gibbs Sampler-Based λ-Dynamics and Rao-Blackwell Estimator for Alchemical Free Energy Calculation. J Chem Theory Comput, 13(6),2501–2510.

Dirar, M, Bilal, N, Ibrahim, ME, & Hamid, M. (2020). Resistance Patterns and Phenotypic Detection of β-lactamase Enzymes among Enterobacteriaceae Isolates from Referral Hospitals in Khartoum State, Sudan. Cureus, 12(3), e7260.

Tooke, CL, Hinchliffe, P, Bragginton, EC, Colenso, KC, Hirvinen, VHA, Takebayashi, Y & Spencer, J. (2019). β-Lactamases and β-Lactamase Inhibitors in the 21st Century. J Mol Biol, 431(18),3472–3500.

Tamma, PD, Doi, Y, Bonomo, RA, Johnson, JK & Simner, PJ. (2019). Antibacterial Resistance Leadership Group. A Primer on AmpC β-Lactamases: Necessary Knowledge for an Increasingly Multidrug-resistant World. Clin Infect Dis, 69(8),1446–1455.

Sawa, T, Kooguchi, K & Moriyama, K. (2020). Molecular diversity of extended-spectrum β-lactamases and carbapenemases, and antimicrobial resistance. J Intensive Care, 8.

Bonomo, RA, Burd, EM, Conly, J, Limbago, BM, Segre, JA & Westblade, LF. (2018). Carbapenemase-Producing Organisms: A Global Scourge. Clin Infect Dis, 66(8), 1290–1297.

Wang, JT, Wu, UI, Lauderdale, TL, Chen, MC, Li, SY, Hsu, LY, & Chang, SC. (2015). Carbapenem-nonsusceptible Enterobacteriaceae in Taiwan. PloS one, 10(3), e0121668.

Chauzy, A, Gaelzer STB, Buyck, J, de Jonge, B, Adier, C, Marchand, S, Couet, W, & Grégoire, N. (2019). Semimechanistic Pharmacodynamic Modeling of Aztreonam-Avibactam Combination to Understand Its Antimicrobial Activity Against Multidrug-Resistant Gram-Negative Bacteria. CPT: pharmacometrics & systems pharmacology, 8(11), 815–824.

Published

01/06/2020

How to Cite

ARAÚJO, L. de L. C.; AZEVEDO, F. H. C. Study of the beta-lactamase enzyme and its relationship with antibiotic resistance. Research, Society and Development, [S. l.], v. 9, n. 7, p. e663974594, 2020. DOI: 10.33448/rsd-v9i7.4594. Disponível em: https://rsdjournal.org/index.php/rsd/article/view/4594. Acesso em: 23 feb. 2024.

Issue

Section

Health Sciences