Abstract
The attenuated Salmonella enterica serovar Typhi strain Ty21a (Ty21a) is the only attenuated live oral vaccine against typhoid fever. Ty21a is also an attractive carrier for the delivery of heterologous antigens. We have used Ty21a for antigen delivery via the hemolysin (HlyA) secretion system of Escherichia coli, the prototype of the type I secretion system (T1SS). In this study, we identified by genetic complementation that the specific mutation of rpoS correlated with the hemolysin production of strain Ty21a. We furthermore showed that complementation with a plasmid encoding rfaH, which is described to be a downstream target of rpoS, led to increased expression and secretion of hemolysin. Finally, we demonstrated a significant enhancement of antibody responses against the heterologous HlyA antigen of Ty21a after immunization of mice with rfaH complemented S. typhi strain secreting HlyA compared with the same strain without rfaH plasmid.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antibodies, Bacterial / blood
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Antigens, Bacterial / genetics
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Antigens, Bacterial / immunology
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Bacterial Proteins / genetics
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Bacterial Proteins / physiology
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Bacterial Vaccines / genetics*
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Bacterial Vaccines / immunology*
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Escherichia coli Proteins / genetics*
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Escherichia coli Proteins / metabolism*
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Genetic Complementation Test
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Hemolysin Proteins / biosynthesis
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Hemolysin Proteins / genetics*
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Hemolysin Proteins / metabolism*
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Mice
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Peptide Elongation Factors / genetics
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Peptide Elongation Factors / metabolism
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Plasmids
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Salmonella typhi / genetics*
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Salmonella typhi / immunology*
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Sigma Factor / genetics
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Sigma Factor / physiology
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Trans-Activators / genetics
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Trans-Activators / metabolism
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Vaccines, Attenuated / genetics
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Vaccines, Attenuated / immunology
Substances
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Antibodies, Bacterial
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Antigens, Bacterial
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Bacterial Proteins
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Bacterial Vaccines
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Escherichia coli Proteins
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Hemolysin Proteins
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Hlya protein, E coli
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Peptide Elongation Factors
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RfaH protein, E coli
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Sigma Factor
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Trans-Activators
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Vaccines, Attenuated
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sigma factor KatF protein, Bacteria