Reconstitution of Gene Network on Penicillin Resistance in E.coli Using Databases Information

Document Type : Original Article

Authors

1 faculty member

2 Lecturer, Research Dept. Of Agronomy and Plant Breeding, Agricultural Research Institute, University of Zabol, Zabol, Iran.

10.35066/J040.2019.701

Abstract

The discovery of penicillin has revolutionized the medical industry and saved thousands of lives. But over time, the resistant bacteria to this antibiotic were identified one after another. Antibiotics of the penicillin family have a β-lactam ring in their molecular structure. By competitively binding to transpeptidase, penicillin and other β-lactam antibiotics inhibit its activity. Inhibition of transpeptidase activity prevents cell wall synthesis and causes bacterial death. Resistant bacteria, have β-lactamase enzyme which has the ability to break the C-N bond in the β-lactam ring. In this study, we reconstructed a network of known β-lactamase genes in E.coli. The results showed that ampC gene plays a central role in induction of resistance in E.coli. Molecular function analysis of other β-lactamase genes showed that β-lactamase activity is only a secondary function for them and their main function is to participate in other unrelated cellular processes. Gene ontology analysis showed that the process of resistance to β-lactam antibiotics was positively correlated with electron transport chain. Also, when exposed to β-lactam antibiotics, the cell membrane is the most active cellular component in E.coli and antibiotic resistance is dependent on the β-lactamase function of cell membrane proteins.

Keywords

References

1- Gaynes R. The Discovery of Penicillin—New Insights After More Than 75 Years of Clinical Use. Emerg Infect Dis. 2017;23(5):849-53.
2- Abraham EP, Chain E. An enzyme from bacteria able to destroy penicillin. 1940. Reviews of infectious diseases. 1988;10(4):677-8.
3- Lobanovska M, Pilla G. Penicillin's Discovery and Antibiotic Resistance: Lessons for the Future? Yale J Biol Med. 2017;90(1):135-45.
4- Kong K-F, Schneper L, Mathee K. Beta-lactam antibiotics: from antibiosis to resistance and bacteriology. APMIS. 2010;118(1):1-36.
5- Typas A, Banzhaf M, Gross CA, Vollmer W. From the regulation of peptidoglycan synthesis to bacterial growth and morphology. Nat Rev Microbiol. 2011;10(2):123-36.
6- Patterson J, Tsilimigras MCB, Livesay DR, Jacobs DJ. Evolution of Stability/Flexibility Relationships in Beta-Lactamase. Biophysical Journal. 2019;116(3):472a.
7- Subedi D, Vijay AK, Willcox M. Overview of mechanisms of antibiotic resistance in Pseudomonas aeruginosa: an ocular perspective. Clinical and Experimental Optometry. 2018;101(2):162-71.
8- Apweiler R, Bairoch A, Wu CH, Barker WC, Boeckmann B, Ferro S, et al. UniProt: the Universal Protein knowledgebase. Nucleic acids research. 2004;32(Database issue):D115-D9.
9- Szklarczyk D, Morris JH, Cook H, Kuhn M, Wyder S, Simonovic M, et al. The STRING database in 2017: quality-controlled protein–protein association networks, made broadly accessible. Nucleic acids research. 2017;45(Database issue):D362-D8.
10- Shannon P, Markiel A, Ozier O, Baliga NS, Wang JT, Ramage D, et al. Cytoscape: a software environment for integrated models of biomolecular interaction networks. Genome research. 2003;13(11):2498-504.
11- Assenov Y, Ramirez F, Schelhorn SE, Lengauer T, Albrecht M. Computing topological parameters of biological networks. Bioinformatics. 2008;24(2):282-4.
12- Shiri Y, Solouki M, Ebrahimie E, Emamjomeh A, Zahiri J. Gibberellin causes wide transcriptional modifications in the early stage of grape cluster development. Genomics. 2019.
13- Shiri Y, Solouki M, Ebrahimie E, Emamjomeh A, Zahiri J. Unraveling the Transcriptional Complexity of Compactness in Sistan Grape Cluster. Plant Science. 2018.
14- Jiao X, Sherman BT, Huang DW, Stephens R, Baseler MW, Lane HC, et al. DAVID-WS: a stateful web service to facilitate gene/protein list analysis. Bioinformatics (Oxford, England). 2012;28(13):1805-6.
15- Benjamini Y, Hochberg Y. Controlling the False Discovery Rate: A Practical and Powerful Approach to Multiple Testing. Journal of the Royal Statistical Society Series B (Methodological). 1995;57(1):289-300.
16- Bush K, Jacoby GA. Updated Functional Classification of β-Lactamases. Antimicrobial Agents and Chemotherapy. 2010;54(3):969-76.
17- Bush K, Jacoby GA, Medeiros AA. A functional classification scheme for beta-lactamases and its correlation with molecular structure. Antimicrobial Agents and Chemotherapy. 1995;39(6):1211-33.
18- Pierrard A, Ledent P, Docquier JD, Feller G, Gerday C, Frère JM. Inducible class C β-lactamases produced by psychrophilic bacteria. FEMS microbiology letters. 1998;161(2):311-5.
19- Horsfall LE, Garau G, Lienard BM, Dideberg O, Schofield CJ, Frere JM, et al. Competitive inhibitors of the CphA metallo-beta-lactamase from Aeromonas hydrophila. Antimicrob Agents Chemother. 2007;51(6):2136-42.
20- Lindquist S, Galleni M, Lindberg F, Normark S. Signalling proteins in enterobacterial AmpC beta-lactamase regulation. Mol Microbiol. 1989;3(8):1091-102.
21- Hesek D, Lee M, Zhang W, Noll BC, Mobashery S. Total synthesis of N-acetylglucosamine-1,6-anhydro-N-acetylmuramylpentapeptide and evaluation of its turnover by AmpD from Escherichia coli. Journal of the American Chemical Society. 2009;131(14):5187-93.
22- Gonzalez-Leiza SM, de Pedro MA, Ayala JA. AmpH, a bifunctional DD-endopeptidase and DD-carboxypeptidase of Escherichia coli. J Bacteriol. 2011;193(24):6887-94.
23- Borisov VB, Murali R, Verkhovskaya ML, Bloch DA, Han H, Gennis RB, et al. Aerobic respiratory chain of Escherichia coli is not allowed to work in fully uncoupled mode. Proceedings of the National Academy of Sciences of the United States of America. 2011;108(42):17320-4.
24- Vega D, Ayala JA. The DD-carboxypeptidase activity encoded by pbp4B is not essential for the cell growth of Escherichia coli. Archives of microbiology. 2006;185(1):23-7.
New Findings in Veterinary Microbiology
Volume 2, Issue 2
April 2020
Pages 1-9

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History

  • Receive Date: 25 December 2019
  • Revise Date: 11 January 2020
  • Accept Date: 19 January 2020

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