https://dspace.nii.res.in//https://dspace.nii.res.in/handle/123456789/1610 Principal Investigator- Dr. G. Senthil Kumar Mon, 27 Apr 2026 15:50:24 GMT 2026-04-27T15:50:24Z https://dspace.nii.res.in:443/retrieve/434c5031-10f8-4e6f-994c-c0de0ef6d246/Dr G Senthil Kumar.JPG https://dspace.nii.res.in//https://dspace.nii.res.in/handle/123456789/1610 https://dspace.nii.res.in//https://dspace.nii.res.in/handle/123456789/1547 Title: Molecular basis of β-lactam antibiotic resistance of ESKAPE bacterium E. faecium Penicillin Binding Protein PBP5 Authors: Hunashal, Yamanappa; Kumar, Ganesan Senthil; Choy, Meng S; 'Andréa, Éverton D D; Santiago, Andre Da Silva; Schoenle, Marta V; Desbonnet, Charlene; Arthur, Michel; Rice, Louis B; Page, Rebecca; Peti, Wolfgang Abstract: Penicillin-binding proteins (PBPs) are essential for the formation of the bacterial cell wall. They are also the targets of β-lactam antibiotics. In Enterococcus faecium, high levels of resistance to β-lactams are associated with the expression of PBP5, with higher levels of resistance associated with distinct PBP5 variants. To define the molecular mechanism of PBP5-mediated resistance we leveraged biomolecular NMR spectroscopy of PBP5 - due to its size (>70 kDa) a challenging NMR target. Our data show that resistant PBP5 variants show significantly increased dynamics either alone or upon formation of the acyl-enzyme inhibitor complex. Furthermore, these variants also exhibit increased acyl-enzyme hydrolysis. Thus, reducing sidechain bulkiness and expanding surface loops results in increased dynamics that facilitates acyl-enzyme hydrolysis and, via increased β-lactam antibiotic turnover, facilitates β-lactam resistance. Together, these data provide the molecular basis of resistance of clinical E. faecium PBP5 variants, results that are likely applicable to the PBP family. Sun, 01 Jan 2023 00:00:00 GMT https://dspace.nii.res.in//https://dspace.nii.res.in/handle/123456789/1547 2023-01-01T00:00:00Z