Abstract
Ralstonia solanacearum is a bacterial phytopathogen of worldwide attention as it causes wilt disease in tomato leading to huge economic loss. This poses a need for identifying host non-specific drug targets to design effective antibacterial agents. Hence, in this study novel therapeutic targets were prioritized by implementing integrative in silico analysis spanning genome to metabolic pathway levels. Initial comparison of chromosome encoded proteins of pathogen against host proteome revealed non-host homologous protein sequences in the pathogen. Further, these proteins were probed for essentiality analysis using database of essential genes as reference, which prioritized the host non-homologous proteins that are essential for survival. Among the 3380 chromosome encoded proteins of the pathogen, 115 were identified as essential and host non-homologous. Subsequent metabolic pathway analysis revealed 24 proteins to be involved in pathogen-specific pathways. On further expression profiling based on codon usage, 17 of these 24 proteins were found to be highly expressed, as per the Codon Adaptation Index (CAI) score. In addition, subcellular localization, virulence factor analysis, drugbank screening and Protein–Protein Interactions (PPIs) were also implemented in order to stringently prioritize the targets based on potentiality and druggability. On cumulative analysis of all these results, 3 unique proteins (Q8XU97, Q8Y1J8 and Q8XVG8) of this pathogen were recognized as highly potential and novel antimicrobial targets. As these proteins resulted from a multilevel stringent prioritization process and were also found to be involved in key survival pathways, these shall form as druggable targets for the design and development of safe bactericidal agents to combat this economically important pathogen.
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Acknowledgements
This research work is supported by a financial grant from the University Grants Commission (UGC), India in the form of UGC Minor Research Project (MRP-6785/16). The authors thank the anonymous reviewers for their valuable inputs.
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University Grants Commission, MRP-6785/16 (GURUNATHAN SUBRAMANIAN)
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Subramanian, G., Vetrivel, U. & Mohamedyousuff, M.I. Deciphering novel potential antibacterial targets in tomato pathogen Ralstonia solanacearum GMI1000 through integration of in silico subtractive genomics, codon usage and protein–protein interaction analyses. Australasian Plant Pathol. 51, 123–133 (2022). https://doi.org/10.1007/s13313-021-00845-6
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DOI: https://doi.org/10.1007/s13313-021-00845-6