Abstract
Universal stress protein A (UspA) is ubiquitously over-expressed in varied species of pathogenic bacteria under stress conditions and helps in cell survival. It is also established as a potential drug target against multidrug-resistant (MDR) uropathogenic Escherichia coli. Till date the mode of action of UspA is unexplored. In this study, in silico approach is undertaken to comprehend UspA function by assimilating its structure-function relationship in ten pathogenic bacteria. This study integrates various computational tools; physicochemical characterization by ProtParam, secondary structure analysis by Psipred, construction of dendrogram by CLAP server, protein-protein interactions (PPIs) using STRING, functional enrichment analysis from protein modules by MCODE in Cytoscape, and 3-D structure prediction by Phyre2. In spite of variances in the amino acid sequences of the ten UspA proteins, their secondary structures, and physiochemical properties are comparable. CLAP tool successfully groups the UspA proteins into two distinct clusters; one that consists of ATP binding domain and another without the ATP binding domain. STRING and MCODE analysis indicated that the former group of UspA proteins is associated with transporter proteins and the latter with cell cycle-related proteins respectively. Discrete structural similarities of UspA proteins in the individual clusters are further verified by their 3D model. Most importantly, results from this study elucidate that although the UspA protein function as a stress responder in different bacterial species, its mode of action at the molecular level is discrete. Additionally, the predicted network of proteins associated with UspA in the different pathogenic bacteria can aid the development of innovative therapies against these pathogens.
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Abbreviations
- UspA:
-
Universal stress protein A
- MDR:
-
Multidrug-resistant
- 3D:
-
Three dimension
- PPIs:
-
Protein-protein interactions
- PIN:
-
Protein-protein interaction network
- STRING:
-
Search Tool for the Retrieval of Interacting Genes/Proteins
- MCODE:
-
Molecular Complex Detection
- GRAVY:
-
grand average of hydropathicity
- CLAP:
-
Classification of Proteins
- LMS:
-
the Local Matching Score
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Acknowledgements
We are grateful to the Director, School of Tropical Medicine, and Prof (Dr.) Bibhuti Saha Head, Department of Tropical Medicine, School of Tropical Medicine, Kolkata West Bengal, India, for their kind support.
Funding
This work was supported by a grant from the Department of Science and Technology, Government of West Bengal (Grant no. 62(Sanc.)/BT/P/Budget/RD-60/2017 dated 12.03.18.
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DB performed the experiments, analyzed the data, and wrote the manuscript and MM further validated the results also edited the final version of the manuscript.
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The present study was approved by the Clinical Research Ethics Committee, School of Tropical Medicine, Kolkata (CREC-STM), Ref no. CREC-STM/250 dated 09/01/15 and informed consent was obtained from all patients for being included in this study.
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Bandyopadhyay, D., Mukherjee, M. Systematic comparison of the protein-protein interaction network of bacterial Universal stress protein A (UspA): an insight into its discrete functions. Biologia 77, 2631–2642 (2022). https://doi.org/10.1007/s11756-022-01102-x
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DOI: https://doi.org/10.1007/s11756-022-01102-x