Salmonella Typhimurium TTSS-2 deficient mig-14 mutant shows attenuation in immunocompromised mice and offers protection against wild-type Salmonella Typhimurium infection
Background Development of Salmonella enterica serovar Typhimurium ( S. Typhimurium) live attenuated vaccine carrier strain to prevent enteric infections has been a subject of intensive study. Several mutants of S . Typhimurium have been proposed as an effective live attenuated vaccine strain. Unfort...
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| Published in | BMC microbiology Vol. 13; no. 1; p. 236 |
|---|---|
| Main Authors | , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
London
BioMed Central
22.10.2013
BioMed Central Ltd |
| Subjects | |
| Online Access | Get full text |
| ISSN | 1471-2180 1471-2180 |
| DOI | 10.1186/1471-2180-13-236 |
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| Abstract | Background
Development of
Salmonella enterica
serovar Typhimurium (
S.
Typhimurium) live attenuated vaccine carrier strain to prevent enteric infections has been a subject of intensive study. Several mutants of
S
. Typhimurium have been proposed as an effective live attenuated vaccine strain. Unfortunately, many such mutant strains failed to successfully complete the clinical trials as they were suboptimal in delivering effective safety and immunogenicity. However, it remained unclear, whether the existing live attenuated
S
. Typhimurium strains can further be attenuated with improved safety and immune efficacy or not.
Results
We deleted a specific non-SPI (Salmonella Pathogenicity Island) encoded virulence factor
mig-14
(an antimicrobial peptide resistant protein) in
ssaV
deficient
S.
Typhimurium strain. The
ssaV
is an important SPI-II gene involved in
Salmonella
replication in macrophages and its mutant strain is considered as a potential live attenuated strain. However, fatal systemic infection was previously reported in immunocompromised mice like
Nos2
−/−
and
Il-10
−/−
when infected with
ssaV
deficient
S
. Typhimurium. Here we reported that attenuation of
S
. Typhimurium
ssaV
mutant in immunocompromised mice can further be improved by introducing additional deletion of gene
mig-14
. The
ssaV, mig-14
double mutant was as efficient as
ssaV
mutant, with respect to host colonization and eliciting
Salmonella
-specific mucosal sIgA and serum IgG response in wild-type C57BL/6 mice. Interestingly, this double mutant did not show any systemic infection in immunocompromised mice.
Conclusions
This study suggests that
ssaV, mig-14
double mutant strain can be effectively used as a potential vaccine candidate even in immunocompromised mice. Such attenuated vaccine strain could possibly used for expression of heterologous antigens and thus for development of a polyvalent vaccine strain. |
|---|---|
| AbstractList | BACKGROUND: Development of Salmonella enterica serovar Typhimurium (S. Typhimurium) live attenuated vaccine carrier strain to prevent enteric infections has been a subject of intensive study. Several mutants of S. Typhimurium have been proposed as an effective live attenuated vaccine strain. Unfortunately, many such mutant strains failed to successfully complete the clinical trials as they were suboptimal in delivering effective safety and immunogenicity. However, it remained unclear, whether the existing live attenuated S. Typhimurium strains can further be attenuated with improved safety and immune efficacy or not. RESULTS: We deleted a specific non-SPI (Salmonella Pathogenicity Island) encoded virulence factor mig-14 (an antimicrobial peptide resistant protein) in ssaV deficient S. Typhimurium strain. The ssaV is an important SPI-II gene involved in Salmonella replication in macrophages and its mutant strain is considered as a potential live attenuated strain. However, fatal systemic infection was previously reported in immunocompromised mice like Nos2−/− and Il-10−/− when infected with ssaV deficient S. Typhimurium. Here we reported that attenuation of S. Typhimurium ssaV mutant in immunocompromised mice can further be improved by introducing additional deletion of gene mig-14. The ssaV, mig-14 double mutant was as efficient as ssaV mutant, with respect to host colonization and eliciting Salmonella-specific mucosal sIgA and serum IgG response in wild-type C57BL/6 mice. Interestingly, this double mutant did not show any systemic infection in immunocompromised mice. CONCLUSIONS: This study suggests that ssaV, mig-14 double mutant strain can be effectively used as a potential vaccine candidate even in immunocompromised mice. Such attenuated vaccine strain could possibly used for expression of heterologous antigens and thus for development of a polyvalent vaccine strain. Development of Salmonella enterica serovar Typhimurium (S. Typhimurium) live attenuated vaccine carrier strain to prevent enteric infections has been a subject of intensive study. Several mutants of S. Typhimurium have been proposed as an effective live attenuated vaccine strain. Unfortunately, many such mutant strains failed to successfully complete the clinical trials as they were suboptimal in delivering effective safety and immunogenicity. However, it remained unclear, whether the existing live attenuated S. Typhimurium strains can further be attenuated with improved safety and immune efficacy or not. We deleted a specific non-SPI (Salmonella Pathogenicity Island) encoded virulence factor mig-14 (an antimicrobial peptide resistant protein) in ssaV deficient S. Typhimurium strain. The ssaV is an important SPI-II gene involved in Salmonella replication in macrophages and its mutant strain is considered as a potential live attenuated strain. However, fatal systemic infection was previously reported in immunocompromised mice like Nos2.sup.-/- and Il-10.sup.-/- when infected with ssaV deficient S. Typhimurium. Here we reported that attenuation of S. Typhimurium ssaV mutant in immunocompromised mice can further be improved by introducing additional deletion of gene mig-14. The ssaV, mig-14 double mutant was as efficient as ssaV mutant, with respect to host colonization and eliciting Salmonella-specific mucosal sIgA and serum IgG response in wild-type C57BL/6 mice. Interestingly, this double mutant did not show any systemic infection in immunocompromised mice. This study suggests that ssaV, mig-14 double mutant strain can be effectively used as a potential vaccine candidate even in immunocompromised mice. Such attenuated vaccine strain could possibly used for expression of heterologous antigens and thus for development of a polyvalent vaccine strain. Development of Salmonella enterica serovar Typhimurium (S. Typhimurium) live attenuated vaccine carrier strain to prevent enteric infections has been a subject of intensive study. Several mutants of S. Typhimurium have been proposed as an effective live attenuated vaccine strain. Unfortunately, many such mutant strains failed to successfully complete the clinical trials as they were suboptimal in delivering effective safety and immunogenicity. However, it remained unclear, whether the existing live attenuated S. Typhimurium strains can further be attenuated with improved safety and immune efficacy or not. We deleted a specific non-SPI (Salmonella Pathogenicity Island) encoded virulence factor mig-14 (an antimicrobial peptide resistant protein) in ssaV deficient S. Typhimurium strain. The ssaV is an important SPI-II gene involved in Salmonella replication in macrophages and its mutant strain is considered as a potential live attenuated strain. However, fatal systemic infection was previously reported in immunocompromised mice like Nos2-/- and Il-10-/- when infected with ssaV deficient S. Typhimurium. Here we reported that attenuation of S. Typhimurium ssaV mutant in immunocompromised mice can further be improved by introducing additional deletion of gene mig-14. The ssaV, mig-14 double mutant was as efficient as ssaV mutant, with respect to host colonization and eliciting Salmonella-specific mucosal sIgA and serum IgG response in wild-type C57BL/6 mice. Interestingly, this double mutant did not show any systemic infection in immunocompromised mice. This study suggests that ssaV, mig-14 double mutant strain can be effectively used as a potential vaccine candidate even in immunocompromised mice. Such attenuated vaccine strain could possibly used for expression of heterologous antigens and thus for development of a polyvalent vaccine strain. Background: Development of Salmonella enterica serovar Typhimurium (S. Typhimurium) live attenuated vaccine carrier strain to prevent enteric infections has been a subject of intensive study. Several mutants of S. Typhimurium have been proposed as an effective live attenuated vaccine strain. Unfortunately, many such mutant strains failed to successfully complete the clinical trials as they were suboptimal in delivering effective safety and immunogenicity. However, it remained unclear, whether the existing live attenuated S. Typhimurium strains can further be attenuated with improved safety and immune efficacy or not. Results: We deleted a specific non-SPI (Salmonella Pathogenicity Island) encoded virulence factor mig-14 (an antimicrobial peptide resistant protein) in ssaV deficient S. Typhimurium strain. The ssaV is an important SPI-II gene involved in Salmonella replication in macrophages and its mutant strain is considered as a potential live attenuated strain. However, fatal systemic infection was previously reported in immunocompromised mice like Nos2 super(-/-) and Il-10 super(-/-) when infected with ssaV deficient S. Typhimurium. Here we reported that attenuation of S. Typhimurium ssaV mutant in immunocompromised mice can further be improved by introducing additional deletion of gene mig-14. The ssaV, mig-14 double mutant was as efficient as ssaV mutant, with respect to host colonization and eliciting Salmonella-specific mucosal sIgA and serum IgG response in wild-type C57BL/6 mice. Interestingly, this double mutant did not show any systemic infection in immunocompromised mice. Conclusions: This study suggests that ssaV, mig-14 double mutant strain can be effectively used as a potential vaccine candidate even in immunocompromised mice. Such attenuated vaccine strain could possibly used for expression of heterologous antigens and thus for development of a polyvalent vaccine strain. Doc number: 236 Abstract Background: Development of Salmonella enterica serovar Typhimurium (S. Typhimurium) live attenuated vaccine carrier strain to prevent enteric infections has been a subject of intensive study. Several mutants of S . Typhimurium have been proposed as an effective live attenuated vaccine strain. Unfortunately, many such mutant strains failed to successfully complete the clinical trials as they were suboptimal in delivering effective safety and immunogenicity. However, it remained unclear, whether the existing live attenuated S . Typhimurium strains can further be attenuated with improved safety and immune efficacy or not. Results: We deleted a specific non-SPI (Salmonella Pathogenicity Island) encoded virulence factor mig-14 (an antimicrobial peptide resistant protein) in ssaV deficient S. Typhimurium strain. The ssaV is an important SPI-II gene involved in Salmonella replication in macrophages and its mutant strain is considered as a potential live attenuated strain. However, fatal systemic infection was previously reported in immunocompromised mice like Nos2-/- and Il-10-/- when infected with ssaV deficient S . Typhimurium. Here we reported that attenuation of S . Typhimurium ssaV mutant in immunocompromised mice can further be improved by introducing additional deletion of gene mig-14 . The ssaV, mig-14 double mutant was as efficient as ssaV mutant, with respect to host colonization and eliciting Salmonella -specific mucosal sIgA and serum IgG response in wild-type C57BL/6 mice. Interestingly, this double mutant did not show any systemic infection in immunocompromised mice. Conclusions: This study suggests that ssaV, mig-14 double mutant strain can be effectively used as a potential vaccine candidate even in immunocompromised mice. Such attenuated vaccine strain could possibly used for expression of heterologous antigens and thus for development of a polyvalent vaccine strain. Development of Salmonella enterica serovar Typhimurium (S. Typhimurium) live attenuated vaccine carrier strain to prevent enteric infections has been a subject of intensive study. Several mutants of S. Typhimurium have been proposed as an effective live attenuated vaccine strain. Unfortunately, many such mutant strains failed to successfully complete the clinical trials as they were suboptimal in delivering effective safety and immunogenicity. However, it remained unclear, whether the existing live attenuated S. Typhimurium strains can further be attenuated with improved safety and immune efficacy or not.BACKGROUNDDevelopment of Salmonella enterica serovar Typhimurium (S. Typhimurium) live attenuated vaccine carrier strain to prevent enteric infections has been a subject of intensive study. Several mutants of S. Typhimurium have been proposed as an effective live attenuated vaccine strain. Unfortunately, many such mutant strains failed to successfully complete the clinical trials as they were suboptimal in delivering effective safety and immunogenicity. However, it remained unclear, whether the existing live attenuated S. Typhimurium strains can further be attenuated with improved safety and immune efficacy or not.We deleted a specific non-SPI (Salmonella Pathogenicity Island) encoded virulence factor mig-14 (an antimicrobial peptide resistant protein) in ssaV deficient S. Typhimurium strain. The ssaV is an important SPI-II gene involved in Salmonella replication in macrophages and its mutant strain is considered as a potential live attenuated strain. However, fatal systemic infection was previously reported in immunocompromised mice like Nos2-/- and Il-10-/- when infected with ssaV deficient S. Typhimurium. Here we reported that attenuation of S. Typhimurium ssaV mutant in immunocompromised mice can further be improved by introducing additional deletion of gene mig-14. The ssaV, mig-14 double mutant was as efficient as ssaV mutant, with respect to host colonization and eliciting Salmonella-specific mucosal sIgA and serum IgG response in wild-type C57BL/6 mice. Interestingly, this double mutant did not show any systemic infection in immunocompromised mice.RESULTSWe deleted a specific non-SPI (Salmonella Pathogenicity Island) encoded virulence factor mig-14 (an antimicrobial peptide resistant protein) in ssaV deficient S. Typhimurium strain. The ssaV is an important SPI-II gene involved in Salmonella replication in macrophages and its mutant strain is considered as a potential live attenuated strain. However, fatal systemic infection was previously reported in immunocompromised mice like Nos2-/- and Il-10-/- when infected with ssaV deficient S. Typhimurium. Here we reported that attenuation of S. Typhimurium ssaV mutant in immunocompromised mice can further be improved by introducing additional deletion of gene mig-14. The ssaV, mig-14 double mutant was as efficient as ssaV mutant, with respect to host colonization and eliciting Salmonella-specific mucosal sIgA and serum IgG response in wild-type C57BL/6 mice. Interestingly, this double mutant did not show any systemic infection in immunocompromised mice.This study suggests that ssaV, mig-14 double mutant strain can be effectively used as a potential vaccine candidate even in immunocompromised mice. Such attenuated vaccine strain could possibly used for expression of heterologous antigens and thus for development of a polyvalent vaccine strain.CONCLUSIONSThis study suggests that ssaV, mig-14 double mutant strain can be effectively used as a potential vaccine candidate even in immunocompromised mice. Such attenuated vaccine strain could possibly used for expression of heterologous antigens and thus for development of a polyvalent vaccine strain. Background Development of Salmonella enterica serovar Typhimurium ( S. Typhimurium) live attenuated vaccine carrier strain to prevent enteric infections has been a subject of intensive study. Several mutants of S . Typhimurium have been proposed as an effective live attenuated vaccine strain. Unfortunately, many such mutant strains failed to successfully complete the clinical trials as they were suboptimal in delivering effective safety and immunogenicity. However, it remained unclear, whether the existing live attenuated S . Typhimurium strains can further be attenuated with improved safety and immune efficacy or not. Results We deleted a specific non-SPI (Salmonella Pathogenicity Island) encoded virulence factor mig-14 (an antimicrobial peptide resistant protein) in ssaV deficient S. Typhimurium strain. The ssaV is an important SPI-II gene involved in Salmonella replication in macrophages and its mutant strain is considered as a potential live attenuated strain. However, fatal systemic infection was previously reported in immunocompromised mice like Nos2 −/− and Il-10 −/− when infected with ssaV deficient S . Typhimurium. Here we reported that attenuation of S . Typhimurium ssaV mutant in immunocompromised mice can further be improved by introducing additional deletion of gene mig-14 . The ssaV, mig-14 double mutant was as efficient as ssaV mutant, with respect to host colonization and eliciting Salmonella -specific mucosal sIgA and serum IgG response in wild-type C57BL/6 mice. Interestingly, this double mutant did not show any systemic infection in immunocompromised mice. Conclusions This study suggests that ssaV, mig-14 double mutant strain can be effectively used as a potential vaccine candidate even in immunocompromised mice. Such attenuated vaccine strain could possibly used for expression of heterologous antigens and thus for development of a polyvalent vaccine strain. Background Development of Salmonella enterica serovar Typhimurium (S. Typhimurium) live attenuated vaccine carrier strain to prevent enteric infections has been a subject of intensive study. Several mutants of S. Typhimurium have been proposed as an effective live attenuated vaccine strain. Unfortunately, many such mutant strains failed to successfully complete the clinical trials as they were suboptimal in delivering effective safety and immunogenicity. However, it remained unclear, whether the existing live attenuated S. Typhimurium strains can further be attenuated with improved safety and immune efficacy or not. Results We deleted a specific non-SPI (Salmonella Pathogenicity Island) encoded virulence factor mig-14 (an antimicrobial peptide resistant protein) in ssaV deficient S. Typhimurium strain. The ssaV is an important SPI-II gene involved in Salmonella replication in macrophages and its mutant strain is considered as a potential live attenuated strain. However, fatal systemic infection was previously reported in immunocompromised mice like Nos2.sup.-/- and Il-10.sup.-/- when infected with ssaV deficient S. Typhimurium. Here we reported that attenuation of S. Typhimurium ssaV mutant in immunocompromised mice can further be improved by introducing additional deletion of gene mig-14. The ssaV, mig-14 double mutant was as efficient as ssaV mutant, with respect to host colonization and eliciting Salmonella-specific mucosal sIgA and serum IgG response in wild-type C57BL/6 mice. Interestingly, this double mutant did not show any systemic infection in immunocompromised mice. Conclusions This study suggests that ssaV, mig-14 double mutant strain can be effectively used as a potential vaccine candidate even in immunocompromised mice. Such attenuated vaccine strain could possibly used for expression of heterologous antigens and thus for development of a polyvalent vaccine strain. |
| ArticleNumber | 236 |
| Audience | Academic |
| Author | Vishwakarma, Vikalp Suar, Mrutyunjay Dash, Sabyasachi Saha, Bhaskar Selvaraj, Sathish kumar Pati, Niladri Bhusan Singh, Neera |
| AuthorAffiliation | 1 School of Biotechnology, KIIT University, Bhubaneswar 751024, Odisha, India 2 National Centre for Cell Science, Ganeshkhind, Pune, India |
| AuthorAffiliation_xml | – name: 1 School of Biotechnology, KIIT University, Bhubaneswar 751024, Odisha, India – name: 2 National Centre for Cell Science, Ganeshkhind, Pune, India |
| Author_xml | – sequence: 1 givenname: Niladri Bhusan surname: Pati fullname: Pati, Niladri Bhusan organization: School of Biotechnology, KIIT University – sequence: 2 givenname: Vikalp surname: Vishwakarma fullname: Vishwakarma, Vikalp organization: School of Biotechnology, KIIT University – sequence: 3 givenname: Sathish kumar surname: Selvaraj fullname: Selvaraj, Sathish kumar organization: National Centre for Cell Science – sequence: 4 givenname: Sabyasachi surname: Dash fullname: Dash, Sabyasachi organization: School of Biotechnology, KIIT University – sequence: 5 givenname: Bhaskar surname: Saha fullname: Saha, Bhaskar organization: National Centre for Cell Science – sequence: 6 givenname: Neera surname: Singh fullname: Singh, Neera organization: School of Biotechnology, KIIT University – sequence: 7 givenname: Mrutyunjay surname: Suar fullname: Suar, Mrutyunjay email: msbiotek@yahoo.com organization: School of Biotechnology, KIIT University |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/24148706$$D View this record in MEDLINE/PubMed |
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| ContentType | Journal Article |
| Copyright | Pati et al.; licensee BioMed Central Ltd. 2013 This article is published under license to BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License ( ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. COPYRIGHT 2013 BioMed Central Ltd. 2013 Pati et al.; licensee BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Copyright © 2013 Pati et al.; licensee BioMed Central Ltd. 2013 Pati et al.; licensee BioMed Central Ltd. |
| Copyright_xml | – notice: Pati et al.; licensee BioMed Central Ltd. 2013 This article is published under license to BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License ( ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. – notice: COPYRIGHT 2013 BioMed Central Ltd. – notice: 2013 Pati et al.; licensee BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. – notice: Copyright © 2013 Pati et al.; licensee BioMed Central Ltd. 2013 Pati et al.; licensee BioMed Central Ltd. |
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| DOI | 10.1186/1471-2180-13-236 |
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| Keywords | MacConkey Agar Plate Vaccine Strain Immunocompromised Mouse Cecal Mucosa Typhimurium Strain |
| Language | English |
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| Snippet | Background
Development of
Salmonella enterica
serovar Typhimurium (
S.
Typhimurium) live attenuated vaccine carrier strain to prevent enteric infections has... Development of Salmonella enterica serovar Typhimurium (S. Typhimurium) live attenuated vaccine carrier strain to prevent enteric infections has been a subject... Background Development of Salmonella enterica serovar Typhimurium (S. Typhimurium) live attenuated vaccine carrier strain to prevent enteric infections has... Doc number: 236 Abstract Background: Development of Salmonella enterica serovar Typhimurium (S. Typhimurium) live attenuated vaccine carrier strain to prevent... Background: Development of Salmonella enterica serovar Typhimurium (S. Typhimurium) live attenuated vaccine carrier strain to prevent enteric infections has... BACKGROUND: Development of Salmonella enterica serovar Typhimurium (S. Typhimurium) live attenuated vaccine carrier strain to prevent enteric infections has... |
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| SubjectTerms | Animal experimentation Animals Antibodies, Bacterial - analysis Antibodies, Bacterial - blood Antigens Bacterial Secretion Systems Biological Microscopy Biomedical and Life Sciences Disease Models, Animal Gastroenteritis Gene Deletion Health aspects Immunity, Mucosal Immunocompromised Host Immunogenicity Immunoglobulin A, Secretory - analysis Immunoglobulin G Immunoglobulin G - blood Life Sciences Medical research Medicine, Experimental Mice Mice, Inbred C57BL Microbe-host interactions and microbial pathogenicity Microbiology Mutants Mycology Parasitology Pathogens Patient outcomes Plasmids Research Article Risk factors Salmonella Salmonella enterica Salmonella Infections, Animal - prevention & control Salmonella typhimurium Salmonella typhimurium - genetics Salmonella typhimurium - immunology Salmonella typhimurium - pathogenicity Salmonella Vaccines - administration & dosage Salmonella Vaccines - adverse effects Salmonella Vaccines - genetics Salmonella Vaccines - immunology Studies Vaccines Vaccines, Attenuated - administration & dosage Vaccines, Attenuated - adverse effects Vaccines, Attenuated - genetics Vaccines, Attenuated - immunology Virology |
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| Title | Salmonella Typhimurium TTSS-2 deficient mig-14 mutant shows attenuation in immunocompromised mice and offers protection against wild-type Salmonella Typhimurium infection |
| URI | https://link.springer.com/article/10.1186/1471-2180-13-236 https://www.ncbi.nlm.nih.gov/pubmed/24148706 https://www.proquest.com/docview/1447954290 https://www.proquest.com/docview/1458539966 https://www.proquest.com/docview/1490764887 http://dx.doi.org/10.1186/1471-2180-13-236 https://pubmed.ncbi.nlm.nih.gov/PMC3819739 |
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