Pathogenicity of Yersinia pestis Synthesis of 1-Dephosphorylated Lipid A
ABSTRACTSynthesis ofEscherichia coliLpxL, which transfers a secondary laurate chain to the 2′ position of lipid A, inYersinia pestisproduced bisphosphoryl hexa-acylated lipid A at 37°C, leading to significant attenuation of virulence. Our previous observations also indicated that strain χ10015(pCD1Ap) (ΔlpxP32::PlpxLlpxL) stimulated a strong inflammatory reaction but sickened mice before recovery and retained virulence via intranasal (i.n.) infection. The development of live, attenuatedY. pestisvaccines may be facilitated by detoxification of its lipopolysaccharide (LPS). Heterologous expression of the lipid A 1-phosphatase, LpxE, fromFrancisella tularensisinY. pestisyields 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 ofY. pestisin mice when it was administered i.n. but actually reduced the 50% lethal dose (LD50) by 3 orders of magnitude when the strain was administered subcutaneously (s.c.). Additionally, LpxE synthesis in wild-typeY. pestisKIM6+(pCD1Ap) led to slight attenuation by s.c. inoculation but no virulence change by i.n. inoculation in mice. In contrast toSalmonella enterica, expression of LpxE does not attenuate the virulence ofY. pestis.