scholarly journals Regulated Delayed Shigella flexneri 2a O-antigen Synthesis in Live Recombinant Salmonella enterica Serovar Typhimurium Induces Comparable Levels of Protective Immune Responses with Constitutive Antigen Synthesis System

Theranostics ◽  
2019 ◽  
Vol 9 (12) ◽  
pp. 3565-3579 ◽  
Author(s):  
Huali Su ◽  
Qing Liu ◽  
Shifeng Wang ◽  
Roy Curtiss ◽  
Qingke Kong
2006 ◽  
Vol 188 (7) ◽  
pp. 2735-2739 ◽  
Author(s):  
Gerald L. Murray ◽  
Stephen R. Attridge ◽  
Renato Morona

ABSTRACT A panel of isogenic Salmonella enterica serovar Typhimurium strains that vary only in the length of the O antigen was constructed through complementation of a wzz double mutant (displaying unregulated O-antigen length) with one of two homologous (wzz ST and wzz fepE) or three heterologous (wzz O139 of Vibrio cholerae and wzz SF and wzz pHS-2 of Shigella flexneri) wzz genes. Each gene was functional in the S. enterica serovar Typhimurium host and specified production of O-antigen polymers with lengths typical of those synthesized by the donor bacteria (ranging from 2 to >100 O-antigen repeat units). By use of this panel of strains, it was found that O-antigen length influences invasion/uptake by macrophage cells; this is the first time this has been shown with Salmonella. O-antigen length was confirmed to be related to complement resistance, with a minimum protective length of >4 and <15 repeat units. O antigen of 16 to 35 repeat units was found to activate complement more efficiently than other lengths, but this was unrelated to complement resistance. No evidence was found to suggest that modifying the length of the O-antigen polymer affected expression of the O1, O4, or O5 antigenic factors.


Microbiology ◽  
2009 ◽  
Vol 155 (10) ◽  
pp. 3403-3410 ◽  
Author(s):  
G. K. Paterson ◽  
D. B. Cone ◽  
S. E. Peters ◽  
D. J. Maskell

The enzyme phosphoglucomutase (Pgm) catalyses the interconversion of glucose 1-phosphate and glucose 6-phosphate and contributes to glycolysis and the generation of sugar nucleotides for biosynthesis. To assess the role of this enzyme in the biology of the pathogen Salmonella enterica serovar Typhimurium we have characterized a pgm deletion mutant in strain SL1344. Compared to SL1344, SL1344 pgm had impaired growth in vitro, was deficient in the ability to utilize galactose as a carbon source and displayed reduced O-antigen polymer length. The mutant was also more susceptible to antimicrobial peptides and showed decreased fitness in the mouse typhoid model. The in vivo phenotype of SL1344 pgm indicated a role for pgm in the early stages of infection, most likely through deficient O-antigen production. Although pgm mutants in other pathogens have potential as live attenuated vaccine strains, SL1344 pgm was not sufficiently attenuated for such use.


2000 ◽  
Vol 68 (6) ◽  
pp. 3116-3120 ◽  
Author(s):  
James J. Kohler ◽  
Latha B. Pathangey ◽  
Sheila R. Gillespie ◽  
Thomas A. Brown

ABSTRACT Recombinant Salmonella strains expressing foreign heterologous genes have been extensively studied as live oral vaccine delivery vectors. We have investigated the mucosal and systemic immune responses following oral immunization with a recombinantSalmonella enterica serovar Typhimurium expressing the hemagglutinin HagB from Porphyromonas gingivalis, a suspected etiological agent of adult periodontal disease. We have previously shown a primary mucosal and systemic response following oral immunization with χ4072/pDMD1 and recall responses following boosting at 14 weeks after primary immunization. In this study, we examined the effects of earlier boosting as well as the effects of deliberately induced immunity to the Salmonella carrier strain on subsequent immune responses. Mice boosted at week 7 following immunization, a point which corresponded to the peak of the primary response, generally showed lower responses than those boosted at week 14. When mice were preimmunized with the Salmonella carrier alone and then immunized with the recombinant strain 7 or 14 weeks later, significant reductions were seen for serum immunoglobulin G (IgG) antibodies at week 14 and for salivary IgA at week 7. No reductions were seen in serum IgA or vaginal wash IgA antibodies. Mice appear to be refractory to boosting with orally administered salmonellae at 7 weeks. Deliberate immunization with the carrier strain did not appreciably affect recall responses at 14 weeks, with the exception of the serum IgG responses, nor did it affect colonization of the Peyer's patches.


2009 ◽  
Vol 77 (6) ◽  
pp. 2568-2575 ◽  
Author(s):  
Karin Ilg ◽  
Kathrin Endt ◽  
Benjamin Misselwitz ◽  
Bärbel Stecher ◽  
Markus Aebi ◽  
...  

ABSTRACT Lipopolysaccharide (LPS) is a major constituent of the outer membrane and an important virulence factor of Salmonella enterica subspecies 1 serovar Typhimurium (serovar Typhimurium). To evaluate the role of LPS in eliciting intestinal inflammation in streptomycin-treated mice, we constructed an O-antigen-deficient serovar Typhimurium strain through deletion of the wbaP gene. The resulting strain was highly susceptible to human complement activity and the antimicrobial peptide mimic polymyxin B. Furthermore, it showed a severe defect in motility and an attenuated phenotype in a competitive mouse infection experiment, where the ΔwbaP strain (SKI12) was directly compared to wild-type Salmonella. Nevertheless, the ΔwbaP strain (SKI12) efficiently invaded HeLa cells in vitro and elicited acute intestinal inflammation in streptomycin-pretreated mice. Our experiments prove that the presence of complete LPS is not essential for in vitro invasion or for triggering acute colitis.


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