Unknown

Dataset Information

0

Deciphering tissue-induced Klebsiella pneumoniae lipid A structure.


ABSTRACT: The outcome of an infection depends on host recognition of the pathogen, hence leading to the activation of signaling pathways controlling defense responses. A long-held belief is that the modification of the lipid A moiety of the lipopolysaccharide could help Gram-negative pathogens to evade innate immunity. However, direct evidence that this happens in vivo is lacking. Here we report the lipid A expressed in the tissues of infected mice by the human pathogen Klebsiella pneumoniae. Our findings demonstrate that Klebsiella remodels its lipid A in a tissue-dependent manner. Lipid A species found in the lungs are consistent with a 2-hydroxyacyl-modified lipid A dependent on the PhoPQ-regulated oxygenase LpxO. The in vivo lipid A pattern is lost in minimally passaged bacteria isolated from the tissues. LpxO-dependent modification reduces the activation of inflammatory responses and mediates resistance to antimicrobial peptides. An lpxO mutant is attenuated in vivo thereby highlighting the importance of this lipid A modification in Klebsiella infection biology. Colistin, one of the last options to treat multidrug-resistant Klebsiella infections, triggers the in vivo lipid A pattern. Moreover, colistin-resistant isolates already express the in vivo lipid A pattern. In these isolates, LpxO-dependent lipid A modification mediates resistance to colistin. Deciphering the lipid A expressed in vivo opens the possibility of designing novel therapeutics targeting the enzymes responsible for the in vivo lipid A pattern.

SUBMITTER: Llobet E 

PROVIDER: S-EPMC4655541 | biostudies-literature | 2015 Nov

REPOSITORIES: biostudies-literature

altmetric image

Publications


The outcome of an infection depends on host recognition of the pathogen, hence leading to the activation of signaling pathways controlling defense responses. A long-held belief is that the modification of the lipid A moiety of the lipopolysaccharide could help Gram-negative pathogens to evade innate immunity. However, direct evidence that this happens in vivo is lacking. Here we report the lipid A expressed in the tissues of infected mice by the human pathogen Klebsiella pneumoniae. Our findings  ...[more]

Similar Datasets

| S-EPMC5444162 | biostudies-literature
| S-EPMC4214298 | biostudies-literature
| S-EPMC3144851 | biostudies-literature
2021-04-09 | GSE112863 | GEO
2017-12-25 | GSE24688 | GEO
| S-EPMC6589860 | biostudies-literature
| S-EPMC4150946 | biostudies-literature
| S-EPMC3129624 | biostudies-literature
| S-EPMC8437966 | biostudies-literature
2023-10-16 | MSV000093124 | MassIVE