Attenuated aroA Salmonella enterica serovar Typhimurium does not induce inflammatory response and early protection of gnotobiotic pigs against parental virulent LT2 strain

Trebichavský, I; Šplı́chalová, Alla; Rychlı́k, Ivan; Hojná, H.; Muneta, Yoshihiro; Mori, Yoshihide; Šplı́chal, Igor

doi:10.1016/j.vaccine.2006.02.054

Cited by 16 publications

(20 citation statements)

References 32 publications

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“…Our results also indicated that aro mutants might be even safer than rough mutants due to their usually higher sensitivity to the antimicrobials tested. This is also supported by observations in gnotobiotic pigs in which rough mutants caused limited damage that led to an induction of an inflammatory immune response, whereas the aroA mutant was so attenuated that it even did not induce any proinflammatory cytokine response (27,33).…”

Section: Discussionsupporting

confidence: 75%

“…In addition, the same phenotype was observed in several other serovar Enteritidis strains into which we transduced the aro mutations. We also tested completely independent transposon mutants from our previous studies (24,33), and in all of the aro mutants we found the same phenotype (data not shown). This clearly demonstrates that the phenotype was tightly associated with the aro mutation and not with only a single strain or serovar.…”

Section: Discussionsupporting

confidence: 63%

“…Although this feature can contribute to the reduced virulence of aro mutants, these mutants may also be defective in motility or respiration, probably due to the inefficient production of ubi-and menaquinones (1,30). Furthermore, when working with aro mutants in serovar Typhimurium in gnotobiotic pigs (33), we observed that the mutants were sensitive to complement killing (unpublished observations). In the present study we therefore focused on the properties of different aro mutants in detail.…”

Section: Discussionmentioning

confidence: 80%

“…The attenuation of serovar Typhimurium aro mutants for gnotobiotic pigs free of any other bacteria also indicated a pleiotropic effect of aro mutation since, at least inside the gut, the aro mutants of serovar Typhimurium should not suffer from a lack of nutrients in the absence of any other competitive microflora. Despite this, the aroA mutant was attenuated and even did not trigger an innate immune response and cytokine production in gnotobiotic pigs (33). This finding suggested that aro mutants not only cannot replicate within a host due to the inability to synthesize aromatic amino acids but may also be defective in cytoplasmic or outer membrane or periplasmic space function, which could make them more sensitive to some components of the innate immune response.…”

mentioning

confidence: 99%

“…aroA and aroD mutants of Salmonella enterica serovar Typhi were successfully tested as a vaccine against human typhoid (31,32), and the same mutations were used also for the construction of avirulent strains for immunization of different farm animals (5,10,22). aro mutants are so attenuated that these mutants are avirulent even for a sensitive model such as gnotobiotic pigs (33). The extreme attenuation was probably a reason why in at least some cases the aro mutants were not immunogenic and did not efficiently protect animals from subsequent infection, especially when highly virulent Salmonella strains were used for the challenge (17,20).…”

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confidence: 99%

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aro Mutations in Salmonella enterica Cause Defects in Cell Wall and Outer Membrane Integrity

et al. 2008

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In this study we characterized aro mutants of Salmonella enterica serovars Enteritidis and Typhimurium, which are frequently used as live oral vaccines. We found that the aroA, aroD, and aroC mutants were sensitive to blood serum, albumen, EDTA, and ovotransferrin, and this defect could be complemented by an appropriate aro gene cloned in a plasmid. Subsequent microarray analysis of gene expression in the aroD mutant in serovar Typhimurium indicated that the reason for this sensitivity might be the upregulation of murA. To confirm this, we artificially overexpressed murA from a multicopy plasmid, and this overexpression caused sensitivity of the strain to albumen and EDTA but not to serum and ovotransferrin. We concluded that attenuation of aro mutants is caused not only by their inability to synthesize aromatic metabolites but also by their defect in cell wall and outer membrane functions associated with decreased resistance to components of innate immune response.

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Section: Discussionsupporting

confidence: 75%

Section: Discussionsupporting

confidence: 63%

Section: Discussionmentioning

confidence: 80%

mentioning

confidence: 99%

mentioning

confidence: 99%

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aro Mutations in Salmonella enterica Cause Defects in Cell Wall and Outer Membrane Integrity

et al. 2008

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Phenotypic characterization, virulence, and immunogenicity of Edwardsiella tarda LSE40 aroA mutant

et al. 2013

Appl Microbiol Biotechnol

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Bacterial aro mutants are frequently used as live attenuated vaccines for domestic animals. In this study, we characterized Edwardsiella tarda strain LSE40 with a deletion in the aroA gene. In addition to autotrophy, the aroA mutant appeared to have delayed cell division and reductions in its swarming motility, biofilm formation, and production of translocator proteins in the type III secretory system. The mutant exhibited high virulence attenuation in turbot fish, Scophthalmus maximus (L.), where the 50 % lethal dose increased by more than 3 log₁₀ via intraperitoneal (i.p.) injection and by >2 log₁₀ via immersion exposure compared with the wild-type parent strain. A tissue persistence study showed that the mutant retained the ability to invade and spread in turbot and viable cells could be detected up to 28 days after i.p. infection and 21 days after immersion exposure. These results suggested a pleiotropic role for aroA in the physiological behavior of E. tarda. Turbot exhibited a good humoral response and the enhanced expression of innate immune factors, interleukin 1β and lysozyme, when vaccinated with aroA mutant at 10⁵ CFU via i.p. injection and at 10⁸ CFU via immersion exposure. However, the aroA mutant did not provide effective protection for turbot against edwardsiellosis following i.p. vaccination at doses of 10⁴-10⁶ CFU or immersion vaccination at doses of 10⁶-10⁸ CFU ml⁻¹. We hypothesized that the aroA mutant did not trigger an appropriate T cell-immune response in turbot against infection of E. tarda.

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Innate immune response in the gut against Salmonella — review

2010

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Innate immunity is shaped by a complex of redundant and pleiotropic factors that ensure recognition, alert and suppression of pathogens. Innate immune responses in the gut are complicated by the requirement of parallel tolerance to commensal microflora predominating in cell numbers and species. In normal individuals, the intestinal mucosa together with relevant lymph nodes represents a robust barrier against systemic spread of non-typhoid Salmonella. Contemporary insights into these defense mechanisms are reviewed.

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Attenuated aroA Salmonella enterica serovar Typhimurium does not induce inflammatory response and early protection of gnotobiotic pigs against parental virulent LT2 strain

Cited by 16 publications

References 32 publications

aro Mutations in Salmonella enterica Cause Defects in Cell Wall and Outer Membrane Integrity

aro Mutations in Salmonella enterica Cause Defects in Cell Wall and Outer Membrane Integrity

Phenotypic characterization, virulence, and immunogenicity of Edwardsiella tarda LSE40 aroA mutant

Innate immune response in the gut against Salmonella — review

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