Protection and immune responses induced by attenuated Salmonella typhimurium UK-1 strains

Xin Zhang, Sandra M. Kelly, Wendy Bollen, Roy Curtiss

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

We previously reported that Salmonella typhimurium SR-11 mutants with deletion mutations in the genes encoding adenylate cyclase (cya) and the cAMP receptor protein (crp) are avirulent and protective in mice. Salmonella typhimurium UK-1 is highly virulent for chicks (oral LD50 of 3 x 103 CFU) and mice (oral LD50 of 8.5 x 103 CFU) and is capable of lethal infections in pigs, calves and horses. We postulated that attenuated derivatives of this lethal strain would probably induce a higher level of protective immunity than achieved with attenuated derivatives of less virulent S. typhimurium strains such as SR11. To test this hypothesis, we have constructed S. typhimurium UK-1 Δcya-12 Δcrp-11 mutant strain (χ)3985 and its virulence plasmid cured derivative (χ)4095 to investigate their avirulence and immunogenicity in mice. We found that the mutants are avirulent and able to induce protective immune responses in BALB/c mice. These mutant strains retained wild-type ability to colonize the gut associated lymphoid tissue but reach and persist in spleen and liver at a significantly lower level than the wild-type parent strain. Mice survived oral infection with > 1 x 109 CFU of (χ)3985 (the equivalent to 105 50% lethal doses of wild-type S. typhimurium UK-1) and were fully protected against challenge with 105 times the LD50 of the wild-type parent. Immunized mice developed a high level of serum IgG titre to Salmonella LPS and delayed-type hypersensitivity (DTH) response to S. typhimurium outer membrane proteins. Compared to the virulence plasmid-containing strain (χ)3985, the virulence plasmid cured Δcya Δcrp mutant strain (χ)4095 was more attenuated and less protective, as some mice immunized with (χ)4095 died when challenged with the wild-type UK-1 strain. This work demonstrates that S. typhimurium UK-1 Δcrp Δcya mutant strain may be a potential live vaccine to induce protective immunity against Salmonella infection or to deliver foreign antigens to the immune system.

Original languageEnglish (US)
Pages (from-to)121-130
Number of pages10
JournalMicrobial Pathogenesis
Volume26
Issue number3
DOIs
StatePublished - Mar 1999
Externally publishedYes

Fingerprint

Salmonella typhimurium
Cyclic AMP Receptor Protein
Lethal Dose 50
Virulence
Plasmids
Immunity
Salmonella Infections
Sequence Deletion
Delayed Hypersensitivity
Lymphoid Tissue
Infection
UK 1
Adenylyl Cyclases
Salmonella
Horses
Immune System
Membrane Proteins
Swine
Vaccines
Spleen

Keywords

  • Δcrp
  • Δcya
  • Attenuated Salmonella vaccine
  • Oral immunization
  • Protective immunity
  • S. typhimurium
  • Splenomegaly
  • Virulence plasmid

ASJC Scopus subject areas

  • Microbiology
  • Infectious Diseases

Cite this

Protection and immune responses induced by attenuated Salmonella typhimurium UK-1 strains. / Zhang, Xin; Kelly, Sandra M.; Bollen, Wendy; Curtiss, Roy.

In: Microbial Pathogenesis, Vol. 26, No. 3, 03.1999, p. 121-130.

Research output: Contribution to journalArticle

Zhang, Xin ; Kelly, Sandra M. ; Bollen, Wendy ; Curtiss, Roy. / Protection and immune responses induced by attenuated Salmonella typhimurium UK-1 strains. In: Microbial Pathogenesis. 1999 ; Vol. 26, No. 3. pp. 121-130.
@article{1786b47e96ad4d698b03102f3f795b05,
title = "Protection and immune responses induced by attenuated Salmonella typhimurium UK-1 strains",
abstract = "We previously reported that Salmonella typhimurium SR-11 mutants with deletion mutations in the genes encoding adenylate cyclase (cya) and the cAMP receptor protein (crp) are avirulent and protective in mice. Salmonella typhimurium UK-1 is highly virulent for chicks (oral LD50 of 3 x 103 CFU) and mice (oral LD50 of 8.5 x 103 CFU) and is capable of lethal infections in pigs, calves and horses. We postulated that attenuated derivatives of this lethal strain would probably induce a higher level of protective immunity than achieved with attenuated derivatives of less virulent S. typhimurium strains such as SR11. To test this hypothesis, we have constructed S. typhimurium UK-1 Δcya-12 Δcrp-11 mutant strain (χ)3985 and its virulence plasmid cured derivative (χ)4095 to investigate their avirulence and immunogenicity in mice. We found that the mutants are avirulent and able to induce protective immune responses in BALB/c mice. These mutant strains retained wild-type ability to colonize the gut associated lymphoid tissue but reach and persist in spleen and liver at a significantly lower level than the wild-type parent strain. Mice survived oral infection with > 1 x 109 CFU of (χ)3985 (the equivalent to 105 50{\%} lethal doses of wild-type S. typhimurium UK-1) and were fully protected against challenge with 105 times the LD50 of the wild-type parent. Immunized mice developed a high level of serum IgG titre to Salmonella LPS and delayed-type hypersensitivity (DTH) response to S. typhimurium outer membrane proteins. Compared to the virulence plasmid-containing strain (χ)3985, the virulence plasmid cured Δcya Δcrp mutant strain (χ)4095 was more attenuated and less protective, as some mice immunized with (χ)4095 died when challenged with the wild-type UK-1 strain. This work demonstrates that S. typhimurium UK-1 Δcrp Δcya mutant strain may be a potential live vaccine to induce protective immunity against Salmonella infection or to deliver foreign antigens to the immune system.",
keywords = "Δcrp, Δcya, Attenuated Salmonella vaccine, Oral immunization, Protective immunity, S. typhimurium, Splenomegaly, Virulence plasmid",
author = "Xin Zhang and Kelly, {Sandra M.} and Wendy Bollen and Roy Curtiss",
year = "1999",
month = "3",
doi = "10.1006/mpat.1998.0245",
language = "English (US)",
volume = "26",
pages = "121--130",
journal = "Microbial Pathogenesis",
issn = "0882-4010",
publisher = "Academic Press Inc.",
number = "3",

}

TY - JOUR

T1 - Protection and immune responses induced by attenuated Salmonella typhimurium UK-1 strains

AU - Zhang, Xin

AU - Kelly, Sandra M.

AU - Bollen, Wendy

AU - Curtiss, Roy

PY - 1999/3

Y1 - 1999/3

N2 - We previously reported that Salmonella typhimurium SR-11 mutants with deletion mutations in the genes encoding adenylate cyclase (cya) and the cAMP receptor protein (crp) are avirulent and protective in mice. Salmonella typhimurium UK-1 is highly virulent for chicks (oral LD50 of 3 x 103 CFU) and mice (oral LD50 of 8.5 x 103 CFU) and is capable of lethal infections in pigs, calves and horses. We postulated that attenuated derivatives of this lethal strain would probably induce a higher level of protective immunity than achieved with attenuated derivatives of less virulent S. typhimurium strains such as SR11. To test this hypothesis, we have constructed S. typhimurium UK-1 Δcya-12 Δcrp-11 mutant strain (χ)3985 and its virulence plasmid cured derivative (χ)4095 to investigate their avirulence and immunogenicity in mice. We found that the mutants are avirulent and able to induce protective immune responses in BALB/c mice. These mutant strains retained wild-type ability to colonize the gut associated lymphoid tissue but reach and persist in spleen and liver at a significantly lower level than the wild-type parent strain. Mice survived oral infection with > 1 x 109 CFU of (χ)3985 (the equivalent to 105 50% lethal doses of wild-type S. typhimurium UK-1) and were fully protected against challenge with 105 times the LD50 of the wild-type parent. Immunized mice developed a high level of serum IgG titre to Salmonella LPS and delayed-type hypersensitivity (DTH) response to S. typhimurium outer membrane proteins. Compared to the virulence plasmid-containing strain (χ)3985, the virulence plasmid cured Δcya Δcrp mutant strain (χ)4095 was more attenuated and less protective, as some mice immunized with (χ)4095 died when challenged with the wild-type UK-1 strain. This work demonstrates that S. typhimurium UK-1 Δcrp Δcya mutant strain may be a potential live vaccine to induce protective immunity against Salmonella infection or to deliver foreign antigens to the immune system.

AB - We previously reported that Salmonella typhimurium SR-11 mutants with deletion mutations in the genes encoding adenylate cyclase (cya) and the cAMP receptor protein (crp) are avirulent and protective in mice. Salmonella typhimurium UK-1 is highly virulent for chicks (oral LD50 of 3 x 103 CFU) and mice (oral LD50 of 8.5 x 103 CFU) and is capable of lethal infections in pigs, calves and horses. We postulated that attenuated derivatives of this lethal strain would probably induce a higher level of protective immunity than achieved with attenuated derivatives of less virulent S. typhimurium strains such as SR11. To test this hypothesis, we have constructed S. typhimurium UK-1 Δcya-12 Δcrp-11 mutant strain (χ)3985 and its virulence plasmid cured derivative (χ)4095 to investigate their avirulence and immunogenicity in mice. We found that the mutants are avirulent and able to induce protective immune responses in BALB/c mice. These mutant strains retained wild-type ability to colonize the gut associated lymphoid tissue but reach and persist in spleen and liver at a significantly lower level than the wild-type parent strain. Mice survived oral infection with > 1 x 109 CFU of (χ)3985 (the equivalent to 105 50% lethal doses of wild-type S. typhimurium UK-1) and were fully protected against challenge with 105 times the LD50 of the wild-type parent. Immunized mice developed a high level of serum IgG titre to Salmonella LPS and delayed-type hypersensitivity (DTH) response to S. typhimurium outer membrane proteins. Compared to the virulence plasmid-containing strain (χ)3985, the virulence plasmid cured Δcya Δcrp mutant strain (χ)4095 was more attenuated and less protective, as some mice immunized with (χ)4095 died when challenged with the wild-type UK-1 strain. This work demonstrates that S. typhimurium UK-1 Δcrp Δcya mutant strain may be a potential live vaccine to induce protective immunity against Salmonella infection or to deliver foreign antigens to the immune system.

KW - Δcrp

KW - Δcya

KW - Attenuated Salmonella vaccine

KW - Oral immunization

KW - Protective immunity

KW - S. typhimurium

KW - Splenomegaly

KW - Virulence plasmid

UR - http://www.scopus.com/inward/record.url?scp=0033103025&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0033103025&partnerID=8YFLogxK

U2 - 10.1006/mpat.1998.0245

DO - 10.1006/mpat.1998.0245

M3 - Article

C2 - 10089152

AN - SCOPUS:0033103025

VL - 26

SP - 121

EP - 130

JO - Microbial Pathogenesis

JF - Microbial Pathogenesis

SN - 0882-4010

IS - 3

ER -