Raw data: Oral vaccine-induced intestinal antibodies select for Salmonella mutants with reduced gut colonization and virulence in mice
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2021-04-06Type
- Data Collection
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Abstract
The ability of gut bacterial pathogens to escape immunity by antigenic variation, particularly via
changes to their cell surface, is a major barrier to immune clearance1. However, not all
bacterial variants are equally fit in all environments2,3. It should therefore be possible to explore such
immune escape mechanisms to direct an evolutionary trade-off towards the selection of less fit
bacterial variants. Here, we demonstrated this phenomenon using Salmonella enterica
subspecies enterica serovar Typhimurium (S.Tm). A dominant surface antigen of S.Tm is its Oantigen,
a long, repetitive glycan that can be rapidly varied by mutations in biosynthetic pathways or
by phase-variation4,5. We quantified the selective advantage of O-antigen variants in the presence
and absence of specific intestinal antibodies (secretory IgA) and identified a set of evolutionary
trajectories allowing immune escape without an associated fitness cost in naïve mice.
Through the use of oral vaccines, we rationally induced IgA responses blocking all of these
trajectories, which selected for Salmonella mutants carrying deletions of the O-antigen polymerase
wzyB. Due to their short O-antigen, these evolved mutants were more susceptible to environmental
stressors (detergents, complement), predation (bacteriophages), and were impaired in gut
colonization and virulence in mice. Therefore, a rationally induced cocktail of intestinal
antibodies can direct an evolutionary trade-off in S.Tm. This lays the foundations for the exploration
of mucosal vaccines capable of setting evolutionary traps as a potential new prophylactic strategy. Show more
Permanent link
https://doi.org/10.3929/ethz-b-000477737Publisher
ETH ZurichSoftware
FCS3 files acquired with a Beckmann Coulter Cytoflex-SSubject
Vaccination, Salmonella, Evolution, O-antigenOrganisational unit
09640 - Wetter Slack, Emma / Wetter Slack, Emma
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