A conditionally lethal mutant of Salmonella Typhimurium induces a protective response in mice

Alejandro A. Hidalgo, Nicolás A. Villagra, Sebastián A. Jerez, Juan A. Fuentes, Guido C. Mora

Resultado de la investigación: Article

1 Cita (Scopus)

Resumen

Here we present the design of a conditionally lethal mutant of Salmonella enterica serovar Typhimurium (S. Typhimurium) which growth depends on tetracycline (Tet). Four mutants of S. Typhimurium, with Tet-conditional growth, were created by inserting the tetRA cassette. Three of the mutants presented a conditional-lethal phenotype in vitro. One mutant in the yabB gene remained conditional inside cells and did not persisted after 24 h in cell cultures. The capacity of S. Typhimurium yabB::tetRA to invade deep organs was investigated in intraperitoneally (IP) infected mice fed with or without chlortetracycline (CTet), a Tet analog with lower antibiotic activity. The yabB::tetRA mutant was undetectable in liver or spleen of animals under normal diet, while in mice under diet including CTet, yabB::tetRA invaded at a level comparable to the WT in mice under normal diet. Moreover, yabB::tetRA produced a strong humoral-immunoresponse after one IP immunization with 106 bacteria, measured as serum reactivity against S. Typhimurium whole cell extract. By contrast, oral immunization with 106 bacteria was weaker and variable on inducing antibodies. Consistently, IP infected mice were fully protected in a challenge with 104 oral S. Typhimurium, while protection was partial in orally immunized mice. Our data indicate that S. Typhimurium yabB::tetRA is a conditionally attenuated strain capable of inducing a protective response in mice in non-permissive conditions.

Idioma originalEnglish
Páginas (desde-hasta)313-318
Número de páginas6
PublicaciónBiochemical and Biophysical Research Communications
Volumen470
N.º2
DOI
EstadoPublished - 5 feb 2016

Huella dactilar

Salmonella
Salmonella typhimurium
Nutrition
Tetracycline
Immunization
Chlortetracycline
Bacteria
Diet
Cell culture
Liver
Animals
Genes
Anti-Bacterial Agents
Salmonella enterica
Antibodies
Growth
Cell Extracts
Serogroup
Spleen
Cell Culture Techniques

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

Citar esto

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title = "A conditionally lethal mutant of Salmonella Typhimurium induces a protective response in mice",
abstract = "Here we present the design of a conditionally lethal mutant of Salmonella enterica serovar Typhimurium (S. Typhimurium) which growth depends on tetracycline (Tet). Four mutants of S. Typhimurium, with Tet-conditional growth, were created by inserting the tetRA cassette. Three of the mutants presented a conditional-lethal phenotype in vitro. One mutant in the yabB gene remained conditional inside cells and did not persisted after 24 h in cell cultures. The capacity of S. Typhimurium yabB::tetRA to invade deep organs was investigated in intraperitoneally (IP) infected mice fed with or without chlortetracycline (CTet), a Tet analog with lower antibiotic activity. The yabB::tetRA mutant was undetectable in liver or spleen of animals under normal diet, while in mice under diet including CTet, yabB::tetRA invaded at a level comparable to the WT in mice under normal diet. Moreover, yabB::tetRA produced a strong humoral-immunoresponse after one IP immunization with 106 bacteria, measured as serum reactivity against S. Typhimurium whole cell extract. By contrast, oral immunization with 106 bacteria was weaker and variable on inducing antibodies. Consistently, IP infected mice were fully protected in a challenge with 104 oral S. Typhimurium, while protection was partial in orally immunized mice. Our data indicate that S. Typhimurium yabB::tetRA is a conditionally attenuated strain capable of inducing a protective response in mice in non-permissive conditions.",
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T1 - A conditionally lethal mutant of Salmonella Typhimurium induces a protective response in mice

AU - Hidalgo, Alejandro A.

AU - Villagra, Nicolás A.

AU - Jerez, Sebastián A.

AU - Fuentes, Juan A.

AU - Mora, Guido C.

PY - 2016/2/5

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N2 - Here we present the design of a conditionally lethal mutant of Salmonella enterica serovar Typhimurium (S. Typhimurium) which growth depends on tetracycline (Tet). Four mutants of S. Typhimurium, with Tet-conditional growth, were created by inserting the tetRA cassette. Three of the mutants presented a conditional-lethal phenotype in vitro. One mutant in the yabB gene remained conditional inside cells and did not persisted after 24 h in cell cultures. The capacity of S. Typhimurium yabB::tetRA to invade deep organs was investigated in intraperitoneally (IP) infected mice fed with or without chlortetracycline (CTet), a Tet analog with lower antibiotic activity. The yabB::tetRA mutant was undetectable in liver or spleen of animals under normal diet, while in mice under diet including CTet, yabB::tetRA invaded at a level comparable to the WT in mice under normal diet. Moreover, yabB::tetRA produced a strong humoral-immunoresponse after one IP immunization with 106 bacteria, measured as serum reactivity against S. Typhimurium whole cell extract. By contrast, oral immunization with 106 bacteria was weaker and variable on inducing antibodies. Consistently, IP infected mice were fully protected in a challenge with 104 oral S. Typhimurium, while protection was partial in orally immunized mice. Our data indicate that S. Typhimurium yabB::tetRA is a conditionally attenuated strain capable of inducing a protective response in mice in non-permissive conditions.

AB - Here we present the design of a conditionally lethal mutant of Salmonella enterica serovar Typhimurium (S. Typhimurium) which growth depends on tetracycline (Tet). Four mutants of S. Typhimurium, with Tet-conditional growth, were created by inserting the tetRA cassette. Three of the mutants presented a conditional-lethal phenotype in vitro. One mutant in the yabB gene remained conditional inside cells and did not persisted after 24 h in cell cultures. The capacity of S. Typhimurium yabB::tetRA to invade deep organs was investigated in intraperitoneally (IP) infected mice fed with or without chlortetracycline (CTet), a Tet analog with lower antibiotic activity. The yabB::tetRA mutant was undetectable in liver or spleen of animals under normal diet, while in mice under diet including CTet, yabB::tetRA invaded at a level comparable to the WT in mice under normal diet. Moreover, yabB::tetRA produced a strong humoral-immunoresponse after one IP immunization with 106 bacteria, measured as serum reactivity against S. Typhimurium whole cell extract. By contrast, oral immunization with 106 bacteria was weaker and variable on inducing antibodies. Consistently, IP infected mice were fully protected in a challenge with 104 oral S. Typhimurium, while protection was partial in orally immunized mice. Our data indicate that S. Typhimurium yabB::tetRA is a conditionally attenuated strain capable of inducing a protective response in mice in non-permissive conditions.

KW - Essential genes

KW - Salmonella vaccine

KW - Tetracycline

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