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PLoS Pathog. 2015 Mar 20;11(3):e1004749. doi: 10.1371/journal.ppat.1004749. eCollection 2015 Mar.

An O antigen capsule modulates bacterial pathogenesis in Shigella sonnei.

Author information

1
Novartis Vaccines Institute for Global Health, Siena, Via Fiorentina, Italy.
2
Institut Pasteur, Unité de Pathogénie Microbienne Moléculaire, INSERM U1202, Paris, France.
3
Wellcome Trust Sanger Institute, Hinxton, Cambridgeshire, United Kingdom.
4
Institut Pasteur, Unité de Pathogénie Microbienne Moléculaire, INSERM U1202, Paris, France; Collège de France, Chaire de Microbiologie et Maladies Infectieuses, Paris, France.

Abstract

Shigella is the leading cause for dysentery worldwide. Together with several virulence factors employed for invasion, the presence and length of the O antigen (OAg) of the lipopolysaccharide (LPS) plays a key role in pathogenesis. S. flexneri 2a has a bimodal OAg chain length distribution regulated in a growth-dependent manner, whereas S. sonnei LPS comprises a monomodal OAg. Here we reveal that S. sonnei, but not S. flexneri 2a, possesses a high molecular weight, immunogenic group 4 capsule, characterized by structural similarity to LPS OAg. We found that a galU mutant of S. sonnei, that is unable to produce a complete LPS with OAg attached, can still assemble OAg material on the cell surface, but a galU mutant of S. flexneri 2a cannot. High molecular weight material not linked to the LPS was purified from S. sonnei and confirmed by NMR to contain the specific sugars of the S. sonnei OAg. Deletion of genes homologous to the group 4 capsule synthesis cluster, previously described in Escherichia coli, abolished the generation of the high molecular weight OAg material. This OAg capsule strongly affects the virulence of S. sonnei. Uncapsulated knockout bacteria were highly invasive in vitro and strongly inflammatory in the rabbit intestine. But, the lack of capsule reduced the ability of S. sonnei to resist complement-mediated killing and to spread from the gut to peripheral organs. In contrast, overexpression of the capsule decreased invasiveness in vitro and inflammation in vivo compared to the wild type. In conclusion, the data indicate that in S. sonnei expression of the capsule modulates bacterial pathogenesis resulting in balanced capabilities to invade and persist in the host environment.

PMID:
25794007
PMCID:
PMC4368438
DOI:
10.1371/journal.ppat.1004749
[Indexed for MEDLINE]
Free PMC Article

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