Evolutionary Relationship of Penicillin-Binding Protein 2 Coding penA Gene and Understanding the Role in Drug-Resistance Mechanism Using Gene Interaction Network Analysis
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The class A β-lactamase penA gene codes for penicillin-binding protein 2 (PBP2) which plays an important role in assembling the peptidoglycans on the outer side of the plasma membrane. The alteration in the structure of PBP2 protein makes the pathogen to gain resistance against penicillin. Thus, it is important to understand the role of drug-resistant mechanism by penA gene to develop potent drugs against penicillin-resistant pathogenic strains. In our study, we have used gene interaction network analysis of penA gene in various bacteria to understand its role in drug-resistant mechanisms. We have collected a total of 1039 interactions from 28 organisms available from STRING database. The penA gene interaction network was constructed using Cytoscape 3.6.1. The network analysis has shown that, along with penA gene, the genes murG, ftsW, murC, ftsA, and ftsQ are observed to have more number of interactors and they may be considered as the key candidates to understand the penA drug-resistant mechanism. Functional enrichment analysis has shown the important GO terms and pathways where penA gene plays an important role. We have also elucidated the evolutionary relationship of penA gene in various Gram-positive and Gram-negative bacteria. Our study helps in understanding the drug-resistant patterns of penA gene in various bacteria and also their evolutionary relationships.
KeywordsPenicillin-binding protein 2 penA gene Antimicrobial resistance Gene interaction network Functional enrichment analysis
The authors gratefully acknowledge the Indian Council of Medical Research (ICMR), Government of India agency for the research grant (IRIS ID: 2014-0099). MSK thanks ICMR for the research fellowship. The authors would like to thank the management of VIT for providing the necessary facilities to carry out this research work.
Conflict of Interest Statement
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