6RCP

Crystal structure of the OmpK36 clinical isolate ST258 from Klebsiella pneumonia

6RCP の概要

• エントリーDOI: 10.2210/pdb6rcp/pdb
• 分子名称: OmpK36 (1 entity in total)
• 機能のキーワード: ompk36 st258, membrane protein
• 由来する生物種: Klebsiella pneumoniae
• タンパク質・核酸の鎖数: 18
• 化学式量合計: 688971.58

構造登録者

Beis, K.,Romano, M.,Kwong, J. (登録日: 2019-04-11, 公開日: 2019-09-11, 最終更新日: 2024-01-24)

主引用文献

Wong, J.L.C.,Romano, M.,Kerry, L.E.,Kwong, H.S.,Low, W.W.,Brett, S.J.,Clements, A.,Beis, K.,Frankel, G.
OmpK36-mediated Carbapenem resistance attenuates ST258 Klebsiella pneumoniae in vivo.
Nat Commun, 10:3957-3957, 2019

PubMed Abstract: Carbapenem-resistance in Klebsiella pneumoniae (KP) sequence type ST258 is mediated by carbapenemases (e.g. KPC-2) and loss or modification of the major non-selective porins OmpK35 and OmpK36. However, the mechanism underpinning OmpK36-mediated resistance and consequences of these changes on pathogenicity remain unknown. By solving the crystal structure of a clinical ST258 OmpK36 variant we provide direct structural evidence of pore constriction, mediated by a di-amino acid (Gly115-Asp116) insertion into loop 3, restricting diffusion of both nutrients (e.g. lactose) and Carbapenems. In the presence of KPC-2 this results in a 16-fold increase in MIC to Meropenem. Additionally, the Gly-Asp insertion impairs bacterial growth in lactose-containing medium and confers a significant in vivo fitness cost in a murine model of ventilator-associated pneumonia. Our data suggests that the continuous selective pressure imposed by widespread Carbapenem utilisation in hospital settings drives the expansion of KP expressing Gly-Asp insertion mutants, despite an associated fitness cost.

PubMed: 31477712
DOI: 10.1038/s41467-019-11756-y

実験手法

X-RAY DIFFRACTION (3.231 Å)