2026-10-14T04:18:23Z https://api.figshare.com/v2/oai

oai:figshare.com:article/33828274 2026-09-16T05:42:13Z category_24352 category_24355 item_type_3 month_year_09_2026

Identification of a Novel ArnT Inhibitor That Restores Polymyxin B Susceptibility in <i>Klebsiella pneumoniae</i> by Blocking Lipid A Modification Song Yongbo (24833242) Bacteriology Infectious agents Polymyxin B Klebsiella pneumoniae ArnT virtual screening Antibiotic adjuvant Lipid A modification <p dir="ltr"><a href="" target="_blank">Polymyxin B is the last resort against the worsening antimicrobial resistance of bacterial, but its clinical application is threatened by drug resistance, particularly in <i>Klebsiella pneumoniae</i>. </a><a href="" target="_blank">Therefore, </a>developing adjuvants that can restore polymyxin B sensitivity is urgently needed. ArnT is a critical lipid A modifying enzyme that alters the surface properties of LPS, thereby inducing resistance to polymyxin B and assisting bacteria in evading attacks from the human immune system. This study used AlphaFold2 to predict the structure of ArnT in <i>K. pneumoniae</i> and the virtual screening from a million-compound library to discovered that nonyl β-D-glucopyranoside (NG) is an effective inhibitor of ArnT. The strong affinity of NG for the ArnT active site, composed of residues I138, L182, E241, R245, and Y316, was verified <i>in vitro</i> and <i>in vivo</i>. It represents the primary mechanism by which NG restores polymyxin B susceptibility in <i>K. pneumoniae</i>. Furthermore, this compound comprehensively enhances the antibacterial efficacy of the antibiotic through multiple synergistic pathways, including strengthening antibiotic-induced membrane damage, disrupting proton motive force homeostasis, inhibiting efflux pump activity, and reducing intracellular ATP supply. These findings identify NG as a potential sensitizer for polymyxin B, providing novel therapeutic strategies and theoretical foundations for treating infections caused by polymyxin-resistant <i>K. pneumoniae</i>.</p> 2026-09-16T05:42:13Z Dataset Dataset 10.6084/m9.figshare.33828274.v1 https://figshare.com/articles/dataset/Identification_of_a_Novel_ArnT_Inhibitor_That_Restores_Polymyxin_B_Susceptibility_in_i_Klebsiella_pneumoniae_i_by_Blocking_Lipid_A_Modification/33828274 CC BY 4.0