Characterization of Two Novel Lipopolysaccharide Phosphoethanolamine Transferases in Pasteurella multocida and Their Role in Resistance to Cathelicidin-2
| Autor: | Mark E Ford, Ben Adler, John D. Boyce, Frank St. Michael, Amy Wright, Marina Harper, Deanna Deveson Lucas, Jianjun Li, Andrew D. Cox |
|---|---|
| Přispěvatelé: | Palmer, Guy H. |
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
medicine.medical_treatment Pasteurella Infections Heptose Cathelicidin Lipid A Factor For Inversion Stimulation Protein cathelicidin Transferase Pasteurella multocida Phylogeny chemistry.chemical_classification biology lipopolysaccharide Nuclear Proteins Blood Proteins Isoenzymes Infectious Diseases Biochemistry Ethanolamines cationic antimicrobial Gram-negative bacteria phosphoethanolamine transferase Immunology Antimicrobial peptides Microbiology 03 medical and health sciences Bacterial Proteins Drug Resistance Bacterial medicine Animals Protein Precursors 3-deoxy-d-manno-octulosonic acid Gene Expression Profiling Computational Biology Galactose Sugar Acids Gene Expression Regulation Bacterial biology.organism_classification Ethanolaminephosphotransferase Heptoses Molecular Pathogenesis 030104 developmental biology chemistry Mutation Parasitology Transcriptome Chickens Bacteria |
| Popis: | The lipopolysaccharide (LPS) produced by the Gram-negative bacterial pathogen Pasteurella multocida has phosphoethanolamine (PEtn) residues attached to lipid A, 3-deoxy- d -manno-octulosonic acid (Kdo), heptose, and galactose. In this report, we show that PEtn is transferred to lipid A by the P. multocida EptA homologue, PetL, and is transferred to galactose by a novel PEtn transferase that is unique to P. multocida called PetG. Transcriptomic analyses indicated that petL expression was positively regulated by the global regulator Fis and negatively regulated by an Hfq-dependent small RNA. Importantly, we have identified a novel PEtn transferase called PetK that is responsible for PEtn addition to the single Kdo molecule (Kdo 1 ), directly linked to lipid A in the P. multocida glycoform A LPS. In vitro assays showed that the presence of a functional petL and petK , and therefore the presence of PEtn on lipid A and Kdo 1 , was essential for resistance to the cationic, antimicrobial peptide cathelicidin-2. The importance of PEtn on Kdo 1 and the identification of the transferase responsible for this addition have not previously been shown. Phylogenetic analysis revealed that PetK is the first representative of a new family of predicted PEtn transferases. The PetK family consists of uncharacterized proteins from a range of Gram-negative bacteria that produce LPS glycoforms with only one Kdo molecule, including pathogenic species within the genera Vibrio , Bordetella , and Haemophilus . We predict that many of these bacteria will require the addition of PEtn to Kdo for maximum protection against host antimicrobial peptides. |
| Databáze: | OpenAIRE |
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