Journal article
Francisella tularensis Schu S4 Lipopolysaccharide Core Sugar and O-Antigen Mutants Are Attenuated in a Mouse Model of Tularemia
Infection and immunity, Vol.82(4), pp.1523-1539
04/2014
DOI: 10.1128/IAI.01640-13
PMCID: PMC3993386
PMID: 24452684
Abstract
The virulence factors mediating
Francisella
pathogenesis are being investigated, with an emphasis on understanding how the organism evades innate immunity mechanisms.
Francisella tularensis
produces a lipopolysaccharide (LPS) that is essentially inert and a polysaccharide capsule that helps the organism to evade detection by components of innate immunity. Using an
F. tularensis
Schu S4 mutant library, we identified strains that are disrupted for capsule and O-antigen production. These serum-sensitive strains lack both capsule production and O-antigen laddering. Analysis of the predicted protein sequences for the disrupted genes (
FTT1236
and
FTT1238c
) revealed similarity to those for
waa
(
rfa
) biosynthetic genes in other bacteria. Mass spectrometry further revealed that these proteins are involved in LPS core sugar biosynthesis and the ligation of O antigen to the LPS core sugars. The 50% lethal dose (LD
50
) values of these strains are increased 100- to 1,000-fold for mice. Histopathology revealed that the immune response to the
F. tularensis
mutant strains was significantly different from that observed with wild-type-infected mice. The lung tissue from mutant-infected mice had widespread necrotic debris, but the spleens lacked necrosis and displayed neutrophilia. In contrast, the lungs of wild-type-infected mice had nominal necrosis, but the spleens had widespread necrosis. These data indicate that murine death caused by wild-type strains occurs by a mechanism different from that by which the mutant strains kill mice. Mice immunized with these mutant strains displayed >10-fold protective effects against virulent type A
F. tularensis
challenge.
Details
- Title: Subtitle
- Francisella tularensis Schu S4 Lipopolysaccharide Core Sugar and O-Antigen Mutants Are Attenuated in a Mouse Model of Tularemia
- Creators
- Jed A Rasmussen - Department of Microbiology, University of Iowa Carver College of Medicine, Iowa City, Iowa, USADeborah M. B Post - The Buck Institute for Age Research, Novato, California, USABradford W Gibson - The Buck Institute for Age Research, Novato, California, USAStephen R Lindemann - Biological Sciences Division/Microbiology, Pacific Northwest National Laboratory, Richland, Washington, USAMichael A Apicella - Department of Microbiology, University of Iowa Carver College of Medicine, Iowa City, Iowa, USADavid K Meyerholz - Department of Pathology, University of Iowa Carver College of Medicine, Iowa City, Iowa, USABradley D Jones - Department of Microbiology, University of Iowa Carver College of Medicine, Iowa City, Iowa, USA
- Resource Type
- Journal article
- Publication Details
- Infection and immunity, Vol.82(4), pp.1523-1539
- Publisher
- American Society for Microbiology
- DOI
- 10.1128/IAI.01640-13
- PMID
- 24452684
- PMCID
- PMC3993386
- ISSN
- 0019-9567
- eISSN
- 1098-5522
- Language
- English
- Date published
- 04/2014
- Academic Unit
- Microbiology and Immunology; Pathology; Internal Medicine
- Record Identifier
- 9984083885402771
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