A phosphoethanolamine transferase specific for the 4′-phosphate residue of Cronobacter sakazakii lipid A

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Abstract

Aims:

Investigate how Cronobacter sakazakii modify their lipid A structure to avoid recognition by the host immune cells.

Methods and Results:

Lipid A modification was observed in C. sakazakii BAA894 grown at pH 5·0 but not pH 7·0. Overexpression of C. sakazakii gene ESA_RS09200 in Escherichia coli W3110 caused a phosphoethanolamine (PEA) modification of lipid A; when ESA_RS09200 was deleted in C. sakazakii BAA894, this lipid A modification disappeared. Lipid A modification was observed in BAA894 grown at pH 5·0 when the 1- phosphate residue of lipid A was removed, but disappeared when the 4′- phosphate residue of lipid A was removed. When ESA_RS16430, the orthologous gene of E. coli pmrA, was deleted in C. sakazakii BAA894, this PEA modification of lipid A was still observed, suggesting that this modification was not regulated by the PmrA-PmrB system. Compared to the wild-type BAA894, ESA_RS09200 deletion mutant showed decreased resistance to cationic antimicrobial peptides (CAMP), increased recognition by TLR4/MD2, decreased ability to invade and persist in mammalian cells.

Conclusions:

ESA_RS09200 in C. sakazakii BAA894 encodes a PEA transferase that specifically adds a PEA to the 4′-phosphate residue of lipid A, but not regulated by the PmrA-PmrB system. PEA modification of lipid A reduces recognition and killing by the host innate immune system.

Significance and Impact of the Study:

This study showed that modification of the lipid A moiety of C. sakazakii with PEA increased resistance to CAMP and recognition of the immune response although signalling of TLR4/MD2 cascade, suggesting that the organism could not successfully evade the host innate immune system without the transference of PEA to its lipid A moiety.

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