The Lipopolysaccharide of Shigella Bacteria as a Virulence Factor

Lindberg, Alf A.; Kärnell, Anders; Weintraub, Andrej

doi:10.1093/clinids/13.supplement_4.s279

Cited by 111 publications

(86 citation statements)

References 17 publications

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“…In other experiments, S. flexneri hybrid strains that express different LPS O-antigens, such as Escherichia coli O8 antigen, were less virulent in the Serény test (Gemski et al, 1972;Sandlin et al, 1996). These results suggested a critical role for LPS O-antigen side chains in Shigella virulence, in addition to the general role of LPS lipid A as an endotoxin to provoke an inflammatory response (Lindberg et al, 1991;Brahmbhatt et al, 1992).…”

Section: Introductionmentioning

confidence: 92%

Effect of mutations in Shigella flexneri chromosomal and plasmid‐encoded lipopolysaccharide genes on invasion and serum resistance

Hong

Payne

1997

Molecular Microbiology

117

120

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SummaryThis study shows that both length and distribution of lipopolysaccharide (LPS) are important for Shigella flexneri invasion and virulence. Mutants were generated in the chromosomal LPS synthesis genes rfa, rfb, and rol, and in a plasmid-encoded O-antigen chain-length regulator, cld pHS-2 . LPS analysis showed that mutations in rfb genes and in a candidate rfaL gene either eliminated the entire O-antigen side chains or produced chains of greatly reduced length. Mutation in a previously unidentified gene, rfaX, affected the LPS core region and resulted in reduced amounts of O-antigen. Mutants defective in cld pHS-2 or rol had different distributions of O-antigen chain lengths. The results of tissue-culture cell invasion and plaque assays, the Seré ny test, and serum-sensitivity assay suggested roles for the different LPS synthesis genes in bacterial survival and virulence; rfaL, rfaX and rfb loci are required for serum resistance and intercellular spread, but not for invasion; cld pHS-2 is required for resistance to serum killing and for full inflammation in the Seré ny test, but not for invasion or intercellular spread, while rol is required for normal invasiveness and plaque formation, but not for serum resistance. Thus, O-antigen synthesis and chain-length regulation genes encoded on both the chromosome and the small plasmid pHS-2 play important roles in S. flexneri invasion and virulence.

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Section: Introductionmentioning

confidence: 92%

Effect of mutations in Shigella flexneri chromosomal and plasmid‐encoded lipopolysaccharide genes on invasion and serum resistance

Hong

Payne

1997

Molecular Microbiology

117

120

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“…The lipopolysaccharide (LPS) of Shigella, a virulence factor 119,120 , consists of a toxic lipid A moiety embedded in the bacterial outer membrane, a core sugar region and an exposed terminal O polysaccharide. Whereas there is little diversity in lipid A and core regions among Shigella, the terminal O polysaccharide structures vary greatly, thereby giving rise to the immunological specificity that results in distinct serotypes (and subserotypes) 4 .…”

Section: Shigella O-antigensmentioning

confidence: 99%

Clinical trials of Shigella vaccines: two steps forward and one step back on a long, hard road

et al. 2007

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More than 50 years of research has yielded numerous Shigella vaccine candidates that have exemplified both the promise of vaccine-induced prevention of shigellosis and the impediments to developing a safe and effective vaccine for widespread use, a goal that has yet to be attained. This Review discusses the most advanced strategies for Shigella vaccine development, the immune responses that are elicited following disease or vaccination, the factors that have accelerated or impeded Shigella vaccine development and our ideas for the way forward.At the end of the 19th century, as epidemics of bacillary dysentery accompanied by high mortality spread across Japan, the young microbiologist Kiyoshi Shiga examined dysenteric stools and isolated a bacterium that was agglutinated by serum from convalescent patients but not from patients with acute disease [1][2][3] (FIG. 1). That bacterium -known today as Shigella dysenteriae 1 -was the first identified member of the genus Shigella. Four Correspondence to M.L. mlevine@medicine.umaryland.edu. Competing interests statement:The authors declare no competing financial interests. Links NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author ManuscriptShigella species (or groups) are now recognized: S. dysenteriae (group A), which has 15 serotypes; Shigella flexneri (group B), which has 14 classical serotypes and subserotypes; Shigella boydii (group C), which has 20 serotypes; and Shigella sonnei (group D), which has single serotype 4 (TABLE 1).There has been resurgent interest in Shigella as a human pathogen, driven by the availability of more precise data on the disease burden 5-8 , emerging antibiotic resistance 9,10 and the fact that mucosally invasive Shigella, which often cause dysentery (gross blood in diarrhoeal stools), are less amenable to the salutary effects of oral rehydration than non-invasive pathogens that cause watery diarrhoea, such as Vibrio cholerae and enterotoxigenic Escherichia coli. The target populations for the use of Shigella vaccines include infants and young children in developing countries (in which the peak incidence occurs at 12-47 months of age and the S. flexneri serotypes predominate) 5-7 .S. dysenteriae 1, which produces Shiga toxin and typically carries R factors that encode resistance to multiple antibodies, waxes and wanes as a cause of epidemic severe disease in the world's least developed countries [11][12][13][14] Few bacterial pathogens have had their pathogenesis or interactions with mammalian tissues elucidated so precisely at the cellular and subcellular levels as Shigella spp. 20,21 Nevertheless, progress in attaining safe and effective Shigella vaccines has faltered. Herein, we review recent and old clinical trials that have evaluated the safety, immunogenicity and efficacy of candidate Shigella vaccines. We relate the bassis for the most popular strategies (BOX 2), the relevance of the different immune responses measured, the factors that have favoured or impeded vaccine development and, most importantly, the less...

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“…The role of LPS as a virulence factor is less well defined. In some cases it has been demonstrated, and in other cases it is suspected, that antibodies against a CPS or LPS Ochain will protect against infection (Lindberg et al 1991, Popoff 1991, Waldor et al 1994, Fulop et al 2001, Coughlin and Bogard 1987, Brahmbhatt et al 1992, Bowden et al 1995.…”

Section: Introductionmentioning

confidence: 99%

Vaccines based on the cell surface carbohydrates of pathogenic bacteria

Jones

2005

An. Acad. Bras. Ciênc.

169

117

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Glycoconjugate vaccines, in which a cell surface carbohydrate from a micro-organism is covalently attached to an appropriate carrier protein are proving to be the most effective means to generate protective immune responses to prevent a wide range of diseases. The technology appears to be generic and applicable to a wide range of pathogens, as long as antibodies against surface carbohydrates help protect against infection. Three such vaccines, against Haemophilus influenzae type b, Neisseria meningitidis Group C and seven serotypes of Streptococcus pneumoniae, have already been licensed and many others are in development.This article discusses the rationale for the development and use of glycoconjugate vaccines, the mechanisms by which they elicit T cell-dependent immune responses and the implications of this for vaccine development, the role of physicochemical methods in the characterisation and quality control of these vaccines, and the novel products which are under development.

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The Lipopolysaccharide of Shigella Bacteria as a Virulence Factor

Cited by 111 publications

References 17 publications

Effect of mutations in Shigella flexneri chromosomal and plasmid‐encoded lipopolysaccharide genes on invasion and serum resistance

Effect of mutations in Shigella flexneri chromosomal and plasmid‐encoded lipopolysaccharide genes on invasion and serum resistance

Clinical trials of Shigella vaccines: two steps forward and one step back on a long, hard road

Vaccines based on the cell surface carbohydrates of pathogenic bacteria

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