6RD3

Crystal structure of the wild type OmpK36 from Klebsiella pneumonia

Summary for 6RD3

• Entry DOI: 10.2210/pdb6rd3/pdb
• Descriptor: OmpK36, (HYDROXYETHYLOXY)TRI(ETHYLOXY)OCTANE, MAGNESIUM ION, ... (4 entities in total)
• Functional Keywords: ompk36 wt, membrane protein
• Biological source: Klebsiella pneumoniae
• Total number of polymer chains: 6
• Total formula weight: 237386.04

Authors

Beis, K.,Romano, M.,Kwong, J. (deposition date: 2019-04-12, release date: 2019-09-11, Last modification date: 2024-01-24)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (1.98 Å)