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Current Drug Discovery Technologies

Editor-in-Chief

ISSN (Print): 1570-1638
ISSN (Online): 1875-6220

Research Article

In silico Study of the Proteins Involved in the Persistence of Brucella spp.

Author(s): Parisa Asadollahi, Nourkhoda Sadeghifard, Hossein Kazemian, Iraj Pakzad* and Behrooz Sadeghi Kalani*

Volume 20, Issue 1, 2023

Published on: 08 September, 2022

Article ID: e050822207324 Pages: 13

DOI: 10.2174/1570163819666220805161821

Price: $65

Abstract

Background: One of the major problems with Brucella infections is its tendency to become chronic and recurrent, providing a hindrance to the management of this infection. It has been proposed that chronicity is greatly affected by a phenomenon called persistence in bacteria. Several mechanisms are involved in bacterial persistence, including the type II toxin-antitoxin system, the SOS and oxidative and stringent responses.

Methods: In this in silico study, these persistence mechanisms in Brucella spp. were investigated.

Results: The structure and the interactions between modules involved in these systems were designed, and novel peptides that can interfere with some of these important mechanisms were developed.

Conclusion: Since peptide-based therapeutics are a new and evolving field due to their ease of production, we hope that peptides developed in this study, as well as the information about the structure and interactions of modules of persistence mechanisms, can further be used to design drugs against Brucella persister cells in the hope of restraining the chronic nature of Brucellosis.

Keywords: Brucella, in silico, brucellosis, protein interaction, inhibitory peptides, zoonotic febrile disease.

Graphical Abstract
[1]
Eskandari-Nasab E, Moghadampour M, Hasani SS, et al. Relationship between γ-interferon gene polymorphisms and susceptibility to brucellosis infection. Microbiol Immunol 2013; 57(11): 785-91.
[http://dx.doi.org/10.1111/1348-0421.12093] [PMID: 24033468]
[2]
Fisher RA, Gollan B, Helaine S. Persistent bacterial infections and persister cells. Nat Rev Microbiol 2017; 15(8): 453-64.
[http://dx.doi.org/10.1038/nrmicro.2017.42] [PMID: 28529326]
[3]
Levin-Reisman I, Ronin I, Gefen O, Braniss I, Shoresh N, Balaban NQ. Antibiotic tolerance facilitates the evolution of resistance. Science 2017; 355(6327): 826-30.
[http://dx.doi.org/10.1126/science.aaj2191] [PMID: 28183996]
[4]
Mohammadzadeh R, Shivaee A, Ohadi E, Kalani BS. In silico insight into the dominant type II toxin-antitoxin systems and Clp proteases in Listeria monocytogenes and designation of derived peptides as a novel approach to interfere with this system. Int J Pept Res Ther 2020; 26(1): 613-23.
[http://dx.doi.org/10.1007/s10989-019-09868-6]
[5]
Amraei F, Narimisa N, Sadeghi Kalani B, Lohrasbi V, Masjedian Jazi F. Persister cells formation and expression of type II Toxin-Antitoxin system genes in Brucella melitensis (16M) and Brucella abortus (B19). Iran J Pathol 2020; 15(2): 127-33.
[http://dx.doi.org/10.30699/ijp.2020.118902.2294] [PMID: 32215028]
[6]
Narimisa N, Sadeghi Kalani B, Mohammadzadeh R, Masjedian Jazi F. Combination of antibiotics-Nisin reduces the formation of Persister cell in Listeria monocytogenes. Microb Drug Resist 2021; 27(2): 137-44.
[http://dx.doi.org/10.1089/mdr.2020.0019] [PMID: 32429732]
[7]
Narimisa N, Amraei F, Kalani BS, Azarnezhad A, Jazi FM. Biofilm establishment, biofilm persister cell formation, and relative gene expression analysis of type II toxin-antitoxin system in Klebsiella pneumoniae. Gene Rep 2020; 21100846
[http://dx.doi.org/10.1016/j.genrep.2020.100846]
[8]
Trastoy R, Manso T, Fernández-García L, et al. Mechanisms of bacterial tolerance and persistence in the gastrointestinal and respiratory environments. Clin Microbiol Rev 2018; 31(4): e00023-18.
[http://dx.doi.org/10.1128/CMR.00023-18] [PMID: 30068737]
[9]
Kalani BS, Irajian G, Lotfollahi L, Abdollahzadeh E, Razavi S. Putative type II toxin-antitoxin systems in Listeria monocytogenes isolated from clinical, food, and animal samples in Iran. Microb Pathog 2018; 122: 19-24.
[http://dx.doi.org/10.1016/j.micpath.2018.06.003] [PMID: 29879433]
[10]
Shivaee A, Mohammadzadeh R, Shahbazi S, Pardakhtchi E, Ohadi E, Kalani BS. Time-variable expression levels of mazF, atlE, sdrH, and bap genes during biofilm formation in Staphylococcus epidermidis. Acta Microbiol Immunol Hung 2019; 66(4): 499-508.
[http://dx.doi.org/10.1556/030.66.2019.019] [PMID: 31198057]
[11]
Zadeh RG, Kalani BS, Ari MM, Talebi M, Razavi S, Jazi FM. Isolation of persister cells within the biofilm and relative gene expression analysis of type II toxin/antitoxin system in Pseudomonas aeruginosa isolates in exponential and stationary phases. J Glob Antimicrob Resist 2022; 28: 30-7.
[http://dx.doi.org/10.1016/j.jgar.2021.11.009] [PMID: 34922056]
[12]
Kaviar VH, Khoshnood S, Asadollahi P, et al. Survey on phenotypic resistance in Enterococcus faecalis: Comparison between the expression of biofilm-associated genes in Enterococcus faecalis persister and non-persister cells. Mol Biol Rep 2022; 49(2): 971-9.
[http://dx.doi.org/10.1007/s11033-021-06915-8] [PMID: 34751916]
[13]
Ronneau S, Helaine S. Clarifying the link between toxin–antitoxin modules and bacterial persistence. J Mol Biol 2019; 431(18): 3462-71.
[http://dx.doi.org/10.1016/j.jmb.2019.03.019] [PMID: 30914294]
[14]
Page R, Peti W. Toxin-antitoxin systems in bacterial growth arrest and persistence. Nat Chem Biol 2016; 12(4): 208-14.
[http://dx.doi.org/10.1038/nchembio.2044] [PMID: 26991085]
[15]
Zamakhaev M, Goncharenko A, Shumkov M. Toxin-antitoxin systems and bacterial persistence. Appl Biochem Microbiol 2019; 55(6): 571-81.
[http://dx.doi.org/10.1134/S0003683819060140]
[16]
Ghafourian S, Raftari M, Sadeghifard N, Sekawi Z. Toxin-antitoxin systems: Classification, biological function and application in biotechnology. Mol Biol 2014; 16(1): 9-14.
[PMID: 23652423]
[17]
Asadollahi P, Pakzad I, Ghafourian S, et al. In silico investigation of lon protease as a promising therapeutic target. Drug Res (Stuttg) 2022; 72(4): 180-8.
[http://dx.doi.org/10.1055/a-1713-3137] [PMID: 35042266]
[18]
Podlesek Z, Žgur Bertok D. The DNA damage inducible SOS response is aa key player in generation of bacterial persister cells and population wide tolerance. Front Microbiol 2020; 11: 1785.
[http://dx.doi.org/10.3389/fmicb.2020.01785] [PMID: 32849403]
[19]
Narimisa N, Amraei F, Kalani BS, Jazi FM. Evaluation of gene expression and protein structural modeling involved in persister cell formation in Salmonella typhimurium. Braz J Microbiol 2021; 52(1): 207-17.
[http://dx.doi.org/10.1007/s42770-020-00388-w] [PMID: 33125683]
[20]
Irving SE, Choudhury NR, Corrigan RM. The stringent response and physiological roles of (pp) pGpp in bacteria. Nat Rev Microbiol 2020; 1-16.
[PMID: 33149273]
[21]
Malathi K, Ramaiah S. Bioinformatics approaches for new drug discovery: A review. Biotechnol Genet Eng Rev 2018; 34(2): 243-60.
[http://dx.doi.org/10.1080/02648725.2018.1502984] [PMID: 30064294]
[22]
Lagunin AA, Goel RK, Gawande DY, et al. Chemo- and bioinformatics resources for in silico drug discovery from medicinal plants beyond their traditional use: A critical review. Nat Prod Rep 2014; 31(11): 1585-611.
[http://dx.doi.org/10.1039/C4NP00068D] [PMID: 25051191]
[23]
Waksman G, Sansom C. Introduction: Proteomics and protein-protein interactions: Biology, chemistry, bioinformatics, and drug design. Proteomics and Protein-Protein Interactions. Springer 2005; pp. 1-18.
[http://dx.doi.org/10.1007/0-387-24532-4_1]
[24]
Sharifi-Rad A, Mehrzad J, Darroudi M, Saberi MR, Chamani J. Oil-in-water nanoemulsions comprising Berberine in olive oil: Biological activities, binding mechanisms to human serum albumin or holo-transferrin and QMMD simulations. J Biomol Struct Dyn 2021; 39(3): 1029-43.
[http://dx.doi.org/10.1080/07391102.2020.1724568] [PMID: 32000592]
[25]
Zare-Feizabadi N, Amiri-Tehranizadeh Z, Sharifi-Rad A, et al. Determining the Interaction behavior of calf thymus DNA with anastrozole in the presence of histone H1: Spectroscopies and cell viability of MCF-7 cell line investigations. DNA Cell Biol 2021; 40(8): 1039-51.
[http://dx.doi.org/10.1089/dna.2021.0052] [PMID: 34165362]
[26]
Sadeghzadeh F, Entezari AA, Behzadian K, et al. Characterizing the binding of angiotensin converting enzyme I inhibitory peptide to human hemoglobin: Influence of electromagnetic fields. Protein Pept Lett 2020; 27(10): 1007-21.
[http://dx.doi.org/10.2174/1871530320666200425203636] [PMID: 32334494]
[27]
Dareini M, Amiri Tehranizadeh Z, Marjani N, et al. A novel view of the separate and simultaneous binding effects of docetaxel and anastrozole with calf thymus DNA: Experimental and in silico approaches. Spectrochim Acta A Mol Biomol Spectrosc 2020; 228117528
[http://dx.doi.org/10.1016/j.saa.2019.117528] [PMID: 31718965]
[28]
Beigoli S, Sharifi Rad A, Askari A, Assaran Darban R, Chamani J. Isothermal titration calorimetry and stopped flow circular dichroism investigations of the interaction between lomefloxacin and human serum albumin in the presence of amino acids. J Biomol Struct Dyn 2019; 37(9): 2265-82.
[http://dx.doi.org/10.1080/07391102.2018.1491421] [PMID: 30047851]
[29]
Marjani N, Dareini M, Asadzade-Lotfabad M, et al. Evaluation of the binding effect and cytotoxicity assay of 2-Ethyl-5-(4-methylphenyl) pyramido pyrazole ophthalazine trione on calf thymus DNA: Spectroscopic, calorimetric, and molecular dynamics approaches. Luminescence 2022; 37(2): 310-22.
[http://dx.doi.org/10.1002/bio.4173] [PMID: 34862709]
[30]
Asadollahi P, Pakzad I, Sadeghifard N, et al. Immunoinformatics insights into the internalin A and B proteins to design a multi-epitope subunit vaccine for L. monocytogenes. Int J Pept Res Ther 2022; 28(1): 1-10.
[http://dx.doi.org/10.1007/s10989-021-10359-w]
[31]
Amraei F, Narimisa N, Sadeghi Kalani B, Mohammadzadeh R, Lohrasbi V, Masjedian Jazi F. The expression of type II TA system genes following exposure to the sub-inhibitory concentration of gentamicin and acid stress in Brucella spp. Microb Pathog 2020; 144: 104194-4.
[http://dx.doi.org/10.1016/j.micpath.2020.104194] [PMID: 32289464]
[32]
HeeShin W. Prediction of protein structure and interaction by GALAXY protein modeling programs. Biodesign 2014; 2: 1-11.
[33]
Colovos C, Yeates TO. Verification of protein structures: Patterns of nonbonded atomic interactions. Protein Sci 1993; 2(9): 1511-9.
[http://dx.doi.org/10.1002/pro.5560020916] [PMID: 8401235]
[34]
Wiederstein M, Sippl MJ. ProSA-web: Interactive web service for the recognition of errors in three-dimensional structures of proteins. Nucleic Acids Res 2007; 35(Web Server issue Suppl. 2): W407-10.
[http://dx.doi.org/10.1093/nar/gkm290] [PMID: 17517781]
[35]
Willard L, Ranjan A, Zhang H, et al. VADAR: A web server for quantitative evaluation of protein structure quality. Nucleic Acids Res 2003; 31(13): 3316-9.
[http://dx.doi.org/10.1093/nar/gkg565] [PMID: 12824316]
[36]
Benkert P, Biasini M, Schwede T. Toward the estimation of the absolute quality of individual protein structure models. Bioinformatics 2011; 27(3): 343-50.
[http://dx.doi.org/10.1093/bioinformatics/btq662] [PMID: 21134891]
[37]
Thomsen R, Christensen MH. MolDock: A new technique for high-accuracy molecular docking. J Med Chem 2006; 49(11): 3315-21.
[http://dx.doi.org/10.1021/jm051197e] [PMID: 16722650]
[38]
Sedan Y, Marcu O, Lyskov S, Schueler-Furman O. Peptiderive server: Derive peptide inhibitors from protein-protein interactions. Nucleic Acids Res 2016; 44(W1)W536-41
[http://dx.doi.org/10.1093/nar/gkw385] [PMID: 27141963]
[39]
Abdollahpour N, Soheili V, Saberi MR, Chamani J. Investigation of the interaction between human serum albumin and two drugs as binary and ternary systems. Eur J Drug Metab Pharmacokinet 2016; 41(6): 705-21.
[http://dx.doi.org/10.1007/s13318-015-0297-y] [PMID: 26328807]
[40]
Chamani J, Moosavi-Movahedi A, Hakimelahi G. Structural changes in β-lactoglobulin by conjugation with three different kinds of carboxymethyl cyclodextrins. Thermochim Acta 2005; 432(1): 106-11.
[http://dx.doi.org/10.1016/j.tca.2005.04.014]
[41]
Snel B, Lehmann G, Bork P, Huynen MA. STRING: A web-server to retrieve and display the repeatedly occurring neighbourhood of a gene. Nucleic Acids Res 2000; 28(18): 3442-4.
[http://dx.doi.org/10.1093/nar/28.18.3442] [PMID: 10982861]
[42]
Ireton K, Mortuza R, Gyanwali GC, Gianfelice A, Hussain M. Role of internalin proteins in pathogenesis of Listeria monocytogenes. Mol Microbiol 2021; 116: 1407-19.
[http://dx.doi.org/10.1111/mmi.14836]
[43]
Liochev SI, Benov L, Touati D, Fridovich I. Induction of the soxRS regulon of Escherichia coli by superoxide. J Biol Chem 1999; 274(14): 9479-81.
[http://dx.doi.org/10.1074/jbc.274.14.9479] [PMID: 10092630 ]

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