11 research outputs found

    Deciphering the Acylation Pattern of Yersinia enterocolitica Lipid A

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    <div><p>Pathogenic bacteria may modify their surface to evade the host innate immune response. <em>Yersinia enterocolitica</em> modulates its lipopolysaccharide (LPS) lipid A structure, and the key regulatory signal is temperature. At 21°C, lipid A is hexa-acylated and may be modified with aminoarabinose or palmitate. At 37°C, <em>Y. enterocolitica</em> expresses a tetra-acylated lipid A consistent with the 3′-O-deacylation of the molecule. In this work, by combining genetic and mass spectrometric analysis, we establish that <em>Y. enterocolitica</em> encodes a lipid A deacylase, LpxR, responsible for the lipid A structure observed at 37°C. Western blot analyses indicate that LpxR exhibits latency at 21°C, deacylation of lipid A is not observed despite the expression of LpxR in the membrane. Aminoarabinose-modified lipid A is involved in the latency. 3-D modelling, docking and site-directed mutagenesis experiments showed that LpxR D31 reduces the active site cavity volume so that aminoarabinose containing Kdo<sub>2</sub>-lipid A cannot be accommodated and, therefore, not deacylated. Our data revealed that the expression of <em>lpxR</em> is negatively controlled by RovA and PhoPQ which are necessary for the lipid A modification with aminoarabinose. Next, we investigated the role of lipid A structural plasticity conferred by LpxR on the expression/function of <em>Y. enterocolitica</em> virulence factors. We present evidence that motility and invasion of eukaryotic cells were reduced in the <em>lpxR</em> mutant grown at 21°C. Mechanistically, our data revealed that the expressions of <em>flhDC</em> and <em>rovA</em>, regulators controlling the flagellar regulon and invasin respectively, were down-regulated in the mutant. In contrast, the levels of the virulence plasmid (pYV)-encoded virulence factors Yops and YadA were not affected in the <em>lpxR</em> mutant. Finally, we establish that the low inflammatory response associated to <em>Y. enterocolitica</em> infections is the sum of the anti-inflammatory action exerted by pYV-encoded YopP and the reduced activation of the LPS receptor by a LpxR-dependent deacylated LPS.</p> </div
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