[2S06a] 23.Protein and Metabolic Engineering

2:45 PM - 3:00 PM JST(5:45 AM - 6:00 AM UTC)

[2PME-03] Evolutionary Analysis of Beta-Lactamases in WHO Priority Pathogens Identifies Conserved Motifs and Positions VIM as an Evolutionary Intermediate Between IMP and NDM

○Ananya Anurag Anand¹, Vidushi Yadav¹, Kshitiz K¹, Sreedevi PC¹, Sarfraz Anwar¹, Sintu Kumar Samanta¹ (1. Indian Institute of Information Technology, Allahabad (India))

Keywords:

Antimicrobial resistance,Beta-lactamases,Evolution,Phylogenetics

Beta-lactamase (BL)-mediated resistance poses a major challenge among priority pathogens listed by the World Health Organization (WHO). This study examines the evolutionary diversification and functional organization of metallo-beta-lactamases (MBLs) and AmpC using an integrative framework combining protein-protein interaction (PPI) network analysis, phylogenetic reconstruction, and comparative domain and motif analysis. Co-evolutionary relationships between BLs and associated resistance-related genes were also assessed. PPI analysis identified NagZ as a predominant interacting partner of BLs in P. aeruginosa and Enterobacteriaceae, suggesting a conserved role in BL-associated regulatory pathways and its relevance as a potential therapeutic target. In contrast, A. baumannii exhibited pronounced interaction network diversity, indicating greater functional heterogeneity. Both chromosomally encoded MBL-fold containing proteins and plasmid-encoded true MBLs showed closer evolutionary relationships between A. baumannii and Enterobacteriaceae, whereas chromosomally encoded BLs, such as AmpC and related genes, clustered more closely between A. baumannii and P. aeruginosa. PFAM domain analysis demonstrated higher conservation of catalytic and substrate-binding domains relative to accessory regions. Conserved sequence motifs, including ASNGLI, were identified across diverse MBLs, suggesting a common targeting strategy across multiple BL families. Notably, comparative inter-MBL analysis demonstrated that VIM occupies an intermediate evolutionary position between IMP and NDM.