Identification of Novel Drug Targets in Xanthomonas citri pv. citri Using Subtractive Genomics and Coevolution Analysis

Author : Tumpa Mahato

Abstract : Citrus canker is a devastating bacCitrus canker is a devastating bacterial disease of citrus crops caused by Xanthomonas citri pv. citri (Xcc), a Gram-negative, rodshaped pathogen possessing a polar flagellum and belonging to the family Xanthomonadaceae. Bacterial plant diseases cause significant agricultural losses worldwide, posing serious challenges to food security. The increasing emergence of antibiotic-resistant Xcc strains has further reduced the effectiveness of existing control measures, emphasizing the urgent need for novel therapeutic targets. In this study, a subtractive genomics approach was employed to identify potential drug targets essential for Xcc survival but absent in the citrus host. The complete Xcc proteome was retrieved from the UniProt database, followed by removal of paralogous sequences. Non-homologous proteins were identified using BLASTp against citrus proteins (e-value < 0.005). Essential proteins were screened using the Database of Essential Genes (DEG) with a stringent threshold (e-value < 0.00001), yielding 750 essential, non-host homologous proteins. Subsequent analyses included metabolic pathway mapping, subcellular localization prediction, and druggability assessment. Eight proteins-GlmU, CheA, RmlD, GspE, FleQ, RpoN, Shk, and SecB- were prioritized as promising drug targets, with RpoN, FleQ, and SecB identified as previously unexplored targets in Xcc. Protein–protein interaction analysis using STRING supported their functional importance. Coevolution analysis via the CoeViz server and active site prediction further validated their suitability for structure-based drug design. These findings provide a strong foundation for developing novel antimicrobial strategies to manage citrus canker effectivelyterial disease of citrus crops caused by Xanthomonas citri pv. citri (Xcc), a Gram-negative, rodshaped pathogen possessing a polar flagellum and belonging to the family Xanthomonadaceae. Bacterial plant diseases cause significant agricultural losses worldwide, posing serious challenges to food security. The increasing emergence of antibiotic-resistant Xcc strains has further reduced the effectiveness of existing control measures, emphasizing the urgent need for novel therapeutic targets. In this study, a subtractive genomics approach was employed to identify potential drug targets essential for Xcc survival but absent in the citrus host. The complete Xcc proteome was retrieved from the UniProt database, followed by removal of paralogous sequences. Non-homologous proteins were identified using BLASTp against citrus proteins (e-value < 0.005). Essential proteins were screened using the Database of Essential Genes (DEG) with a stringent threshold (e-value < 0.00001), yielding 750 essential, non-host homologous proteins. Subsequent analyses included metabolic pathway mapping, subcellular localization prediction, and druggability assessment. Eight proteins-GlmU, CheA, RmlD, GspE, FleQ, RpoN, Shk, and SecB- were prioritized as promising drug targets, with RpoN, FleQ, and SecB identified as previously unexplored targets in Xcc. Protein–protein interaction analysis using STRING supported their functional importance. Coevolution analysis via the CoeViz server and active site prediction further validated their suitability for structure-based drug design. These findings provide a strong foundation for developing novel antimicrobial strategies to manage citrus canker effectively

Keywords : Citrus canker, Xanthomonas citri pv. citri, drug target proteins, subtractive genomics, computational biology.

Conference Name : International Conference on AI and Computational Biology (ICAICB-26)

Conference Place : Kolkata, India

Conference Date : 24th Jan 2026