ArticleProceedings of the National Academy of Sciences of the United States of America2015
Deciphering tissue-induced Klebsiella pneumoniae lipid A structure.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers.
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Who cites it
62 citing papers in PubMed, 101 citations in OpenAlex.
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- How Klebsiella pneumoniae controls its virulence.PLoS pathogens · 2025Review
- O-antigen polysaccharides inMicrobiology and molecular biology reviews : MMBR · 2025Review
- MALDI-TOF lipidomics rapidly detects modification of 2-hydroxymyristate lipid A, a potential virulence trait inMicrobiology spectrum · 2025Article
- Phage therapy for Klebsiella pneumoniae: Understanding bacteria-phage interactions for therapeutic innovations.PLoS pathogens · 2025Review
- Insights into the roles of macrophages in Klebsiella pneumoniae infections: a comprehensive review.Cellular & molecular biology letters · 2025Review
- Bacteriophage therapy: a possible alternative therapy against antibiotic-resistant strains ofFrontiers in microbiology · 2025Review
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- Molecular Mechanisms of Bacterial Resistance to Antimicrobial Peptides in the Modern Era: An Updated Review.Microorganisms · 2024Review
- DivergentmBio · 2024Article
- Immunometabolic control byImmunometabolism (Cobham, Surrey) · 2023Review
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- Expanding Knowledge of Methylotrophic Capacity: Structure and Properties of the Rough-Type Lipopolysaccharide fromJACS Au · 2023Article
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- Polymyxin Resistance and Heteroresistance Are Common in Clinical Isolates ofMicrobiology spectrum · 2023Article
- LipidA-IDER to Explore the Global Lipid A Repertoire of Drug-Resistant Gram-Negative Bacteria.Analytical chemistry · 2023Article
- Bacterial extracellular vesicles: towards realistic models for bacterial membranes in molecular interaction studies by surface plasmon resonance.Frontiers in molecular biosciences · 2023Article
2 more citing papers are in PubMed but not listed here.
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Authors and funding
14 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
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.
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