Molecular basis for the increased polymyxin susceptibility of Klebsiella pneumoniae strains with under-acylated lipid A:

Innate Immunity

TonyVelkov¹ 

关键词: Polymyxin;    Klebsiella pneumoniae;    lipopolysaccharide;   

DOI  :  10.1177/1753425912459092

学科分类：生物科学（综合）

来源: Sage Journals

【 摘 要 】

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 1H NMR, using a paired wild type (WT) and the ΔlpxM mutant strains B5055 and B5055ΔlpxM, which predominantly express LPS with hexa- and penta-acylated lipid A structures respectively. LPS from B5055ΔlpxM 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 B5055ΔlpxM 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 B5055ΔlpxM may be attributable to the favorable insertion of polymyxins into the more fluid OM compared with B5055. Mole...

【 授权许可】

CC BY