Grey variants of the live vaccine strain of Francisella tularensis lack lipopolysaccharide O-antigen, show reduced ability to survive in macrophages and do not induce protective immunity in mice

Hartley, G. G.; Taylor, Robin N. Klupp; Prior, John T.; Newstead, Sarah L.; Hitchen, Paul G.; Morris, Howard R.; Dell, Anne; Titball, Richard W.

doi:10.1016/j.vaccine.2005.08.075

Cited by 43 publications

(71 citation statements)

References 23 publications

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“…However, the 59 and 39 ends of the Oantigen locus were found to be bordered by the transposase and pseudotransposase IS sequences isftu2 and isftu1, respectively. The presence of these IS sequences may cause the O-antigen locus to be a hypermutable region, resulting in loss of O antigen (the grey colony variant; Hartley et al, 2005), or phase variation to a F. novicida-type O antigen (Cowley et al, 1996).…”

Section: Discussionmentioning

confidence: 99%

“…However, the LPS O antigen from this mutant did not react with antiserum to F. novicida or to the parent strain. Another concern was that mutant WbtI G191V was a 'grey' colony variant, which has also been reported to lack O antigen (Hartley et al, 2005). There were many phenotypic similarities between the LVS greycolony variant and WbtI G191V .…”

Section: Discussionmentioning

confidence: 99%

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Attenuation and protective efficacy of an O-antigen-deficient mutant of Francisella tularensis LVS

Ryder

Mandal

et al. 2007

Microbiology

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Francisella tularensis is a zoonotic, Gram-negative coccobacillus that causes tularemia in humans and animals. F. tularensis subspecies tularensis (type A) and F. tularensis subspecies holarctica (type B) are antigenically similar and more virulent than Francisella novicida in humans. The genetic locus that encodes the LPS O antigen was found to be substantially different between the type B live vaccine strain (LVS) and F. novicida. One LVS-specific gene with homology to a galactosyl transferase was selected for allelic replacement using a sacB-chloramphenicol expression suicide plasmid, and recombinants were screened for colony morphology on Congo red agar that matched that of F. novicida. Two mutants (WbtI S187Y and WbtI G191V ) were isolated that contained substitutions in conserved motifs in the sugar transamine/perosamine synthetase (WbtI) of the O-antigen locus, and the latter mutant was extensively tested and characterized. WbtI G191V grew at the same rate as the parent strain in Chamberlain's defined medium, completely lacked O antigen, was serum-sensitive but could grow in a mouse macrophage cell line, had increased resistance to sodium deoxycholate, and was highly attenuated in mice. Complementation of WbtI G191V with the wild-type wbtI gene in trans restored normal LPS synthesis, phenotypic properties similar to the parent, and virulence in mice. Immunization with WbtI G191V protected mice against a relatively low-dose intraperitoneal challenge with LVS, but was less protective against a high-dose challenge. These results indicate that complete loss of O antigen alters the surface phenotype and abrogates virulence in F. tularensis, but also compromises the induction of full protective immunity against F. tularensis infection in mice.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Attenuation and protective efficacy of an O-antigen-deficient mutant of Francisella tularensis LVS

Ryder

Mandal

et al. 2007

Microbiology

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“…Nevertheless, in future studies it will be important to compare directly the ability of F. tularensis subspecies to infect different types of mononuclear phagocytes including alveolar macrophages in the presence and absence of opsonins and to assess whether infection efficiency is modulated by surface virulence factors such as capsule or LPS. In this regard it is of interest that both capsule-deficient organisms and LPS-phase variants are serum sensitive (36,66,105,112). Moreover, diminished O-antigen content impairs virulence in mice and reduces survival in macrophages in vitro (36,66).…”

Section: Receptors and Phagocytosis-internalization Of Microbes And Pmentioning

confidence: 99%

“…In this regard it is of interest that both capsule-deficient organisms and LPS-phase variants are serum sensitive (36,66,105,112). Moreover, diminished O-antigen content impairs virulence in mice and reduces survival in macrophages in vitro (36,66).…”

Section: Receptors and Phagocytosis-internalization Of Microbes And Pmentioning

confidence: 99%

“…Finally, the role of capsule and LPS in intramacrophage survival has not been defined precisely. Strains with rough LPS survive poorly in mice and macrophages (36,37,66), but whether phagosome maturation is affected directly has not been determined. The reduced fitness of these organisms may be indirect and may reflect membrane perturbations introduced by the membrane attack complex of the complement cascade.…”

Section: Receptors and Phagocytosis-internalization Of Microbes And Pmentioning

confidence: 99%

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Francisella tularensis:Taxonomy, Genetics, and Immunopathogenesis of a Potential Agent of Biowarfare

McLendon

Apicella

Allen

2006

Annu. Rev. Microbiol.

205

292

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Tularemia is a zoonosis of humans caused by infection with the facultative intracellular bacterium Francisella tularensis. Interest in F. tularensis has increased markedly in the past few years because of its potential use as an agent of bioterrorism. Five subspecies of this organism are found in the Northern hemisphere, but only F. tularensis subsp. tularensis and subsp. holarctica cause disease in humans. This review summarizes what is known about the pathogenesis of tularemia with a focus on bacterial surface components such as lipopolysaccharide and capsule as well as information obtained from the F. tularensis subsp. tularensis SCHU S4 genome. In particular, the mechanisms of action of recently identified virulence factors are discussed in the context of bacterial replication in macrophages and manipulation of the host inflammatory response. Throughout this report shared and unique features of F. tularensis subsp. tularensis, subsp. holarctica, and subsp. novicida are discussed.

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Analysis of carbohydrates and glycoconjugates by matrix‐assisted laser desorption/ionization mass spectrometry: An update for the period 2005–2006

Harvey

2010

Mass Spectrometry Reviews

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This review is the fourth update of the original review, published in 1999, on the application of MALDI mass spectrometry to the analysis of carbohydrates and glycoconjugates and brings coverage of the literature to the end of 2006. The review covers fundamental studies, fragmentation of carbohydrate ions, method developments, and applications of the technique to the analysis of different types of carbohydrate. Specific compound classes that are covered include carbohydrate polymers from plants, N- and O-linked glycans from glycoproteins, glycated proteins, glycolipids from bacteria, glycosides, and various other natural products. There is a short section on the use of MALDI-TOF mass spectrometry for the study of enzymes involved in glycan processing, a section on industrial processes, particularly the development of biopharmaceuticals and a section on the use of MALDI-MS to monitor products of chemical synthesis of carbohydrates. Large carbohydrate-protein complexes and glycodendrimers are highlighted in this final section.

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Grey variants of the live vaccine strain of Francisella tularensis lack lipopolysaccharide O-antigen, show reduced ability to survive in macrophages and do not induce protective immunity in mice

Cited by 43 publications

References 23 publications

Attenuation and protective efficacy of an O-antigen-deficient mutant of Francisella tularensis LVS

Attenuation and protective efficacy of an O-antigen-deficient mutant of Francisella tularensis LVS

Francisella tularensis:Taxonomy, Genetics, and Immunopathogenesis of a Potential Agent of Biowarfare

Analysis of carbohydrates and glycoconjugates by matrix‐assisted laser desorption/ionization mass spectrometry: An update for the period 2005–2006

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