Pathogenicity of Yersinia pestis synthesis of 1-dephosphorylated lipid A

Wei Sun, David A. Six, C. Michael Reynolds, Hak Suk Chung, Christian R H Raetz, Roy Curtiss

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

Abstract

Synthesis of Escherichia coli LpxL, which transfers a secondary laurate chain to the 2' position of lipid A, in Yersinia pestis produced bisphosphoryl hexa-acylated lipid A at 37°C, leading to significant attenuation of virulence. Our previous observations also indicated that strain χ10015(pCD1Ap) (δlpxP32::PlpxL lpxL) stimulated a strong inflammatory reaction but sickened mice before recovery and retained virulence via intranasal (i.n.) infection. The development of live, attenuated Y. pestis vaccines may be facilitated by detoxification of its lipopolysaccharide (LPS). Heterologous expression of the lipid A 1-phosphatase, LpxE, from Francisella tularensis in Y. pestis 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 Y. pestis in 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-type Y. pestis KIM6+(pCD1Ap) led to slight attenuation by s.c. inoculation but no virulence change by i.n. inoculation in mice. In contrast to Salmonella enterica, expression of LpxE does not attenuate the virulence of Y. pestis.

Original languageEnglish (US)
Pages (from-to)1172-1185
Number of pages14
JournalInfection and immunity
Volume81
Issue number4
DOIs
StatePublished - Apr 2013

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Immunology
  • Infectious Diseases

Fingerprint Dive into the research topics of 'Pathogenicity of Yersinia pestis synthesis of 1-dephosphorylated lipid A'. Together they form a unique fingerprint.

Cite this