Characterization of Pseudomonas aeruginosa LpxT reveals dual positional lipid A kinase activity and co‐ordinated control of outer membrane modification. Issue 3 (30th September 2014)

• Record Type: Journal Article
• Authors: Nowicki, Emily M.; O'Brien, John P.; Brodbelt, Jennifer S.; Trent, M. Stephen
• Is Part Of: Molecular microbiology. Volume 94:Issue 3(2014)
• Page Start: 728
• Page End: 741
• Publication Date: 2014-09-30
• Subjects: Molecular microbiology -- Periodicals; 572.829
• DOI: 10.1111/mmi.12796
• Languages: English
• ISSNs: 0950-382X

Abstract

<abstract abstract-type="main"> <title>Summary</title> <p>Gram‐negative bacteria have evolved modification machinery to promote a dynamic outer membrane in response to a continually fluctuating environment. The kinase LpxT, for example, adds a phosphate group to the lipid A moiety of some Gram‐negatives including <italic>E</italic><italic>scherichia coli</italic> and <italic>S</italic><italic>almonella enterica</italic>. LpxT activity is inhibited under conditions that compromise membrane integrity, resulting instead in the addition of positively charged groups to lipid A that increase membrane stability and provide resistance to cationic antimicrobial peptides. We have now identified a functional <italic>lpxT</italic> orthologue in <italic>P</italic><italic>. aeruginosa</italic>. LpxT<sub>Pa</sub> has unique enzymatic characteristics, as it is able to phosphorylate <italic>P</italic><italic>. aeruginosa</italic> lipid A at two sites of the molecule. Surprisingly, a previously uncharacterized lipid A 4′‐dephospho‐1‐triphosphate species was detected. LpxT<sub>Pa</sub> activity is inhibited by magnesium independently of <italic>lpxT</italic><sub>Pa</sub> transcription. Modulation of LpxT<sub>Pa</sub> activity is influenced by transcription of the lipid A aminoarabinose transferase ArnT, known to be activated in response to limiting magnesium. These results demonstrate a divergent activity of LpxT<sub>Pa</sub>, and suggest the existence of a co‐ordinated regulatory mechanism that permits adaptation to a changing environment.</p> </abstract>