Characterization of Two Novel Lipopolysaccharide Phosphoethanolamine Transferases in Pasteurella multocidaand Their Role in Resistance to Cathelicidin-2

التفاصيل البيبلوغرافية
العنوان: Characterization of Two Novel Lipopolysaccharide Phosphoethanolamine Transferases in Pasteurella multocidaand Their Role in Resistance to Cathelicidin-2
المؤلفون: Harper, Marina, Wright, Amy, St. Michael, Frank, Li, Jianjun, Deveson Lucas, Deanna, Ford, Mark, Adler, Ben, Cox, Andrew D., Boyce, John D.
المصدر: Infection and Immunity; August 2017, Vol. 85 Issue: 11
مستخلص: ABSTRACTThe lipopolysaccharide (LPS) produced by the Gram-negative bacterial pathogen Pasteurella multocidahas 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. multocidaEptA homologue, PetL, and is transferred to galactose by a novel PEtn transferase that is unique to P. multocidacalled PetG. Transcriptomic analyses indicated that petLexpression 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 (Kdo1), directly linked to lipid A in the P. multocidaglycoform A LPS. In vitroassays showed that the presence of a functional petLand petK, and therefore the presence of PEtn on lipid A and Kdo1, was essential for resistance to the cationic, antimicrobial peptide cathelicidin-2. The importance of PEtn on Kdo1and 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.
قاعدة البيانات: Supplemental Index
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