Proper expression of the O-antigen of lipopolysaccharide is essential for the virulence ofYersinia enterocoliticaO:8 in experimental oral infection of rabbits

Abstract

The O-antigen of lipopolysaccharide (LPS) is required for virulence in Yersinia enterocolitica serotype O:8. Here we evaluated the importance of controlling the O-antigen biosynthesis using an in vivo rabbit model of infection. Y. enterocolitica O:8 wild-type strain was compared to three mutants differing in the O-antigen phenotype: (i) the rough strain completely devoid of the O-antigen, (ii) the wzy strain that lacks the O-antigen polymerase (Wzy protein) and expresses LPS with only one repeat unit, and (iii) the wzz strain that lacks the O-antigen chain length determinant (Wzz protein) and expresses LPS without modal distribution of O-antigen chain lengths. The most attenuated strain was the wzz mutant. The wzz bacteria were cleared from the tissues by day 30, the blood parameters were least dramatic and histologically only immunomorphological findings were seen. The level of attenuation of the rough and the wzy strain bacteria was between the wild-type and the wzz strain. Wild-type bacteria were highly resistant to killing by polymorphonuclear leukocytes, the wzz strain bacteria were most sensitive and the rough and wzy strain bacteria were intermediate resistant. These results clearly demonstrated that the presence of O-antigen on the bacterial surface is not alone sufficient for full virulence, but also there is a requirement for its controlled chain length.

Comparison of the course of infection of virulent Yersinia enterocolitica serotype O:8 with an isogenic sodA mutant in the peroral rabbit model

“…In the sodA mutant strain, the expression of manganese-superoxide dismutase is abolished and should not confer protection from oxidative damage caused by exposure to leukocytes. Our results show that the sodA mutant was noticeably more sensitive towards leukocytes probably due to the sodA mutation in contrast to the LPS mutant strains (Najdenski et al, 2003a). Previously, this has been shown also with human leukocytes (Roggenkamp et al, 1997).…”

“…On the other hand, there are several case reports on Yersinia-caused meningitis and encephalopathy (Cover and Aber, 1989;Berner et al, 1998). In our previous examination on the importance of controlling the O-antigen biosynthesis (using also an in vivo rabbit model of infection), we established lower brain loading with sodA and DwzzGB mutant strains of Y. enterocolitica O:8 in comparison with other lipopolysaccharide (LPS) mutant strains R2 and DwbcEGB (Najdenski et al, 2003a).…”

Nonreducing Terminal Modifications Determine the Chain Length of Polymannose O Antigens of Escherichia coli and Couple Chain Termination to Polymer Export via an ATP-binding Cassette Transporter

“…Mutations in wzz make Salmonella enterica serovar Typhimurium (11), E. coli O75 (36), and Shigella dysenteriae serotype 2a (37) sensitive to complement and avirulent. Yersinia enterocolitica O:8 mutants with unregulated chain length are sensitive to killing by polymorphonuclear leukocytes and are attenuated for virulence (38). In S. dysenteriae 2a, Wzz creates precise modal O-PS chain length that is critical for the surface exposure of IcsA and therefore influences actin-based motility and intercell invasion (37, 39 -42).…”

Expression of the Yersinia enterocolitica pYV-Encoded Type III Secretion System Is Modulated by Lipopolysaccharide O-Antigen Status

“…The latter include invasin (Inv) (23,24), phospholipase A (YplA) (26), and iron-sequestering proteins (7), and their role in the virulence of Y. enterocolitica has been established. Our group has demonstrated the importance of lipopolysaccharide (LPS) O antigen in virulence in different animal models (1,21,33). The O-antigen mutant (referred to below as YeO8-R) used in these studies was isolated as a spontaneous mutant resistant to the Y. enterocolitica O:8 bacteriophage 80-18 (33).…”