Taxonomic group: bacteria / Proteobacteria
(Phylum: Proteobacteria)
Host organism: Homo sapiens
Associated disease: pneumonia [ICD11:
CA40 
];
urinary tract infections (UTI) [ICD11:
GC08 ];
liver abscess [ICD11:
DB90.0 , ICD11:
SA04 ];
infection due to Klebsiella pneumoniae [ICD11:
XN741 ]
NCBI PubMed ID: 23008349Publication DOI: 10.1177/1753425912459092Journal NLM ID: 101469670Publisher: Sage Publications
Correspondence: jian.li
monash.edu
Institutions: Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Australia
The impact of under-acylation of lipid A on the interaction between Klebsiella pneumoniae LPS and polymyxins B and E was examined with fluorometric and calorimetric methods, and by (1)H NMR, using a paired wild type (WT) and the ∆lpxM mutant strains B5055 and B5055∆lpxM, which predominantly express LPS with hexa- and penta-acylated lipid A structures respectively. LPS from B5055∆lpxM displayed a fourfold increased binding affinity for polymyxins B and E compared with the B5055 WT LPS. EC50 values were consistent with polymyxin minimum inhibitory concentration (MIC) values for each strain. Accordingly, polymyxin exposure considerably enhanced the permeability of the B5055∆lpxM OM. Analysis of the melting profiles of isolated LPS aggregates suggested that bactericidal polymyxin activity may relate to the acyl chains' phase of the outer membrane (OM). The enhanced polymyxin susceptibility of B5055∆lpxM may be attributable to the favorable insertion of polymyxins into the more fluid OM compared with B5055. Molecular models of the polymyxin B-lipid A complex illuminate the key role of the lipid A acyl chains for complexation of polymyxin. The data provide important insight into the molecular basis for the increased polymyxin susceptibility of K. pneumoniae strains with under-acylated lipid A. Under-acylation appears to facilitate the integration of the N-terminal fatty-acyl chain of polymyxin into the OM resulting in an increased susceptibility to its antimicrobial activity/activities.
Lipopolysaccharide, Klebsiella pneumoniae, polymyxin
Structure type: oligomer
Location inside paper: p.275, fig.8, Polymyxin B1-ΔlpxMB5055 Lipid A
Compound class: lipid A
Contained glycoepitopes: IEDB_135394,IEDB_135515,IEDB_141181,IEDB_141807,IEDB_151531
Methods: 1H NMR, SDS-PAGE, biophysical methods, NMR-1D, molecular modeling
Biological activity: investigation the influence of the lipid A acylation pattern on the crucial interaction between K. pneumoniae LPS and polymyxins
Comments, role: mutant strain K. pneumoniae B5055ΔlpxM
3D data: 3D data
Related record ID(s): 29372
NCBI Taxonomy refs (TaxIDs): 573
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There is only one chemically distinct structure:
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