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      • Pathogenicity of <i>Yersinia pestis</i> Synthesis of 1-Dephosphorylated Lipid A

        Sun, Wei,Six, David A.,Reynolds, C. Michael,Chung, Hak Suk,Raetz, Christian R. H.,Curtiss 3rd, Roy American Society for Microbiology 2013 Infection and immunity Vol.81 No.4

        <P>Synthesis of <I>Escherichia coli</I> LpxL, which transfers a secondary laurate chain to the 2′ position of lipid A, in <I>Yersinia pestis</I> produced bisphosphoryl hexa-acylated lipid A at 37°C, leading to significant attenuation of virulence. Our previous observations also indicated that strain χ10015(pCD1Ap) (Δ<I>lpxP32</I>::P<SUB>lpxL</SUB> <I>lpxL</I>) stimulated a strong inflammatory reaction but sickened mice before recovery and retained virulence via intranasal (i.n.) infection. The development of live, attenuated <I>Y. pestis</I> vaccines may be facilitated by detoxification of its lipopolysaccharide (LPS). Heterologous expression of the lipid A 1-phosphatase, LpxE, from <I>Francisella tularensis</I> in <I>Y. pestis</I> yields predominantly 1-dephosphorylated lipid A, as confirmed by mass spectrometry. Results indicated that expression of LpxE on top of LpxL provided no significant reduction in virulence of <I>Y. pestis</I> in mice when it was administered i.n. but actually reduced the 50% lethal dose (LD<SUB>50</SUB>) by 3 orders of magnitude when the strain was administered subcutaneously (s.c.). Additionally, LpxE synthesis in wild-type <I>Y. pestis</I> KIM6+(pCD1Ap) led to slight attenuation by s.c. inoculation but no virulence change by i.n. inoculation in mice. In contrast to <I>Salmonella enterica</I>, expression of LpxE does not attenuate the virulence of <I>Y. pestis</I>.</P>

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