title: An O antigen capsule modulates bacterial pathogenesis in Shigella sonnei.
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.
authors: Novartis Vaccines Institute for Global Health, Siena, Via Fiorentina, Italy.
authors: Mariaelena
authors: M
authors: Caboni
authors: Institut Pasteur, Unité de Pathogénie Microbienne Moléculaire, INSERM U1202, Paris, France.
authors: Thierry
authors: T
authors: Pédron
authors: Novartis Vaccines Institute for Global Health, Siena, Via Fiorentina, Italy.
authors: Omar
authors: O
authors: Rossi
authors: Wellcome Trust Sanger Institute, Hinxton, Cambridgeshire, United Kingdom.
authors: David
authors: D
authors: Goulding
authors: Wellcome Trust Sanger Institute, Hinxton, Cambridgeshire, United Kingdom.
authors: Derek
authors: D
authors: Pickard
authors: Novartis Vaccines Institute for Global Health, Siena, Via Fiorentina, Italy.
authors: Francesco
authors: F
authors: Citiulo
authors: Novartis Vaccines Institute for Global Health, Siena, Via Fiorentina, Italy.
authors: Calman A
authors: CA
authors: MacLennan
authors: Wellcome Trust Sanger Institute, Hinxton, Cambridgeshire, United Kingdom.
authors: Gordon
authors: G
authors: Dougan
authors: Wellcome Trust Sanger Institute, Hinxton, Cambridgeshire, United Kingdom.
authors: Nicholas R
authors: NR
authors: Thomson
authors: Novartis Vaccines Institute for Global Health, Siena, Via Fiorentina, Italy.
authors: Allan
authors: A
authors: Saul
authors: Institut Pasteur, Unité de Pathogénie Microbienne Moléculaire, INSERM U1202, Paris, France; Collège de France, Chaire de Microbiologie et Maladies Infectieuses, Paris, France.
authors: Philippe J
authors: PJ
authors: Sansonetti
authors: Novartis Vaccines Institute for Global Health, Siena, Via Fiorentina, Italy.
authors: Christiane
authors: C
authors: Gerke
mesh_terms: D000818:Animals; D016667:Bacterial Capsules / Q000235:genetics / Q000378:metabolism*; D055785:Gene Knockdown Techniques; D019081:O Antigens / Q000096:biosynthesis* / Q000235:genetics; D011817:Rabbits; D012764:Shigella sonnei / Q000235:genetics / Q000378:metabolism* / Q000472:pathogenicity*
chemical_list: D019081:O Antigens