Characterization of two novel lipopolysaccharide phosphoethanolamine transferases in Pasteurella multocida and their role in resistance to cathelicidin-2

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DOIResolve DOI: https://doi.org/10.1128/IAI.00557-17
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EditorSearch for: Palmer, Guy H.
Name affiliation
  1. National Research Council Canada. Human Health Therapeutics
FormatText
TypeArticle
Journal titleInfection and Immunity
ISSN0019-9567
1098-5522
Volume85
Issue11
Article numbere00557-17
Pages# of pages: 16
Subjectlipopolysaccharide; phosphoethanolamine transferase; Pasteurella multocida; 3-deoxy-d-manno-octulosonic acid; cathelicidin; cationic antimicrobial
Abstract
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 (Kdo1), 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 Kdo1, was essential for resistance to the cationic, antimicrobial peptide cathelicidin-2. The importance of PEtn on Kdo1 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.
Publication date
PublisherAmerican Society for Microbiology
LanguageEnglish
Peer reviewedYes
NPARC number23002638
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