scholarly journals Salmonella enterica Serovar Typhimurium trxA Mutants Are Protective against Virulent Challenge and Induce Less Inflammation than the Live-Attenuated Vaccine Strain SL3261

2009 ◽  
Vol 78 (1) ◽  
pp. 326-336 ◽  
Author(s):  
S. E. Peters ◽  
G. K. Paterson ◽  
E. S. D. Bandularatne ◽  
H. C. Northen ◽  
S. Pleasance ◽  
...  
Keyword(s):  
Vaccine Strain ◽  
Salmonella Enterica ◽  
Parent Strain ◽  
Reductase Activity ◽  
Gene Cassette ◽  
Kanamycin Resistance ◽  
Live Attenuated Vaccine ◽  
Attenuated Vaccine ◽  
Oxidative Stresses ◽  
Serovar Typhimurium

ABSTRACT In Salmonella enterica serovar Typhimurium, trxA encodes thioredoxin 1, a small, soluble protein with disulfide reductase activity, which catalyzes thiol disulfide redox reactions in a variety of substrate proteins. Thioredoxins are involved as antioxidants in defense against oxidative stresses, such as exposure to hydrogen peroxide and hydroxyl radicals. We have made a defined, complete deletion of trxA in the mouse-virulent S. Typhimurium strain SL1344 (SL1344 trxA), replacing the gene with a kanamycin resistance gene cassette. SL1344 trxA was attenuated for virulence in BALB/c mice by the oral and intravenous routes and when used in immunization experiments provided protection against challenge with the virulent parent strain. SL1344 trxA induced less inflammation in murine spleens and livers than SL3261, the aroA mutant, live attenuated vaccine strain. The reduced splenomegaly observed following infection with SL1344 trxA was partially attributed to a reduction in the number of both CD4+ and CD8+ T cells and B lymphocytes in the spleen and reduced infiltration by CD11b+ cells into the spleen compared with spleens from mice infected with SL3261. This less severe pathological response indicates that a trxA mutation might be used to reduce reactogenicity of live attenuated vaccine strains. We tested this by deleting trxA in SL3261. SL3261 trxA was also less inflammatory than SL3261 but was slightly less effective as a vaccine strain than either the SL3261 parent strain or SL1344 trxA.

scholarly journals Osmoregulated periplasmic glucans of Salmonella enterica serovar Typhimurium are required for optimal virulence in mice

Microbiology ◽  
2009 ◽  
Vol 155 (1) ◽  
pp. 229-237 ◽  
Author(s):  
Arvind A. Bhagwat ◽  
Won Jun ◽  
Liu Liu ◽  
Porteen Kannan ◽  
Mahesh Dharne ◽  
...  
Keyword(s):  
Salmonella Enterica ◽  
Type Strain ◽  
Wild Type Strain ◽  
Gene Cassette ◽  
Growth Conditions ◽  
Kanamycin Resistance ◽  
Wild Type ◽  
Serovar Typhimurium ◽  
Resistance Gene Cassette ◽  
Reduced Rate

We purified osmoregulated periplasmic glucans (OPGs) from Salmonella enterica serovar Typhimurium and found them to be composed of 100 % glucose with 2-linked glucose as the most abundant residue, with terminal glucose, 2,3-linked and 2,6-linked glucose also present in high quantities. The two structural genes for OPG biosynthesis, opgG and opgH, form a bicistronic operon, and insertion of a kanamycin resistance gene cassette into this operon resulted in a strain devoid of OPGs. The opgGH mutant strain was impaired in motility and growth under low osmolarity conditions. The opgGH mutation also resulted in a 2 log increase in the LD50 in mice compared to the wild-type strain SL1344. Inability to synthesize OPGs had no significant impact on the organism's lipopolysaccharide pattern or its ability to survive antimicrobial peptides-, detergent-, pH- and nutrient-stress conditions. We observed that the opgGH-defective strain respired at a reduced rate under acidic growth conditions (pH 5.0) and had lower ATP levels compared to the wild-type strain. These data indicate that OPGs of S. Typhimurium contribute towards mouse virulence as well as growth and motility under low osmolarity growth conditions.

scholarly journals Salmonella enterica serovar Typhimurium mutants completely lacking the F0F1 ATPase are novel live attenuated vaccine strains

Vaccine ◽  
2010 ◽  
Vol 28 (4) ◽  
pp. 940-949 ◽  
Author(s):  
H. Northen ◽  
G.K. Paterson ◽  
F. Constantino-Casas ◽  
C.E. Bryant ◽  
S. Clare ◽  
...  
Keyword(s):  
Salmonella Enterica ◽  
Salmonella Enterica Serovar Typhimurium ◽  
Live Attenuated Vaccine ◽  
Attenuated Vaccine ◽  
Serovar Typhimurium

scholarly journals Evaluation of Salmonella enterica Serovar Typhimurium TTSS-2 Deficient fur Mutant as Safe Live-Attenuated Vaccine Candidate for Immunocompromised Mice

PLoS ONE ◽  
2012 ◽  
Vol 7 (12) ◽  
pp. e52043 ◽  
Author(s):  
Vikalp Vishwakarma ◽  
Niladri Bhusan Pati ◽  
Himanshu Singh Chandel ◽  
Sushree Sangeeta Sahoo ◽  
Bhaskar Saha ◽  
...  
Keyword(s):  
Salmonella Enterica ◽  
Salmonella Enterica Serovar Typhimurium ◽  
Vaccine Candidate ◽  
Live Attenuated Vaccine ◽  
Attenuated Vaccine ◽  
Serovar Typhimurium ◽  
Immunocompromised Mice

scholarly journals Improving Our Understanding of Salmonella enterica Serovar Paratyphi B through the Engineering and Testing of a Live Attenuated Vaccine Strain

mSphere ◽  
2018 ◽  
Vol 3 (6) ◽  
Author(s):  
Ellen E. Higginson ◽  
Girish Ramachandran ◽  
Tracy H. Hazen ◽  
Dane A. Kania ◽  
David A. Rasko ◽  
...  
Keyword(s):  
Vaccine Strain ◽  
Salmonella Enterica ◽  
Enteric Fever ◽  
Sensu Stricto ◽  
Live Attenuated Vaccine ◽  
Content Type ◽  
Heterologous Challenge ◽  
Paratyphi B ◽  
Homologous Challenge ◽  
Ideal Vaccine

ABSTRACT Enteric fever is caused by three Salmonella enterica serovars: Typhi, Paratyphi A, and Paratyphi B sensu stricto. Although vaccines against two of these serovars are licensed (Typhi) or in clinical development (Paratyphi A), as yet there are no candidates for S. Paratyphi B. To gain genomic insight into these serovars, we sequenced 38 enteric fever-associated strains from Chile and compared these with reference genomes. Each of the serovars was separated genomically based on the core genome. Genomic comparisons identified loci that were aberrant between serovars Paratyphi B sensu stricto and Paratyphi B Java, which is typically associated with gastroenteritis; however, the majority of these were annotated as hypothetical or phage related and thus were not ideal vaccine candidates. With the genomic information in hand, we engineered a live attenuated S. Paratyphi B sensu stricto vaccine strain, CVD 2005, which was capable of protecting mice from both homologous challenge and heterologous challenge with S. Paratyphi B Java. These findings extend our understanding of S. Paratyphi B and provide a viable vaccine option for inclusion in a trivalent live attenuated enteric fever vaccine formulation. IMPORTANCE We developed a live attenuated Salmonella enterica serovar Paratyphi B vaccine that conferred protection in mice against challenge with S. Paratyphi B sensu stricto and S. Paratyphi B Java, which are the causes of enteric fever and gastroenteritis, respectively. Currently, the incidence of invasive S. Paratyphi B sensu stricto infections is low; however, the development of new conjugate vaccines against other enteric fever serovars could lead to the emergence of S. Paratyphi B to fill the niche left by these other pathogens. As such, an effective S. Paratyphi B vaccine would be a useful tool in the armamentarium against Salmonella infections. Comparative genomics confirmed the serovar-specific groupings of these isolates and revealed that there are a limited number of genetic differences between the sensu stricto and Java strains, which are mostly hypothetical and phage-encoded proteins. The observed level of genomic similarity likely explains why we observe some cross-protection.

scholarly journals A DIVA vaccine strain lacking RpoS and the secondary messenger c-di-GMP for protection against salmonellosis in pigs

2020 ◽  
Vol 51 (1) ◽  
Author(s):  
Carmen Gil ◽  
Cristina Latasa ◽  
Enrique García-Ona ◽  
Isidro Lázaro ◽  
Javier Labairu ◽  
...  
Keyword(s):  
Vaccine Strain ◽  
Serological Test ◽  
Oral Route ◽  
Infection Model ◽  
Cell Mediated Immunity ◽  
Protective Effects ◽  
The European Union ◽  
Live Attenuated Vaccine ◽  
Secondary Messenger ◽  
Serovar Typhimurium

AbstractSalmonellosis is the second most common food-borne zoonosis in the European Union, with pigs being a major reservoir of this pathogen. Salmonella control in pig production requires multiple measures amongst which vaccination may be used to reduce subclinical carriage and shedding of prevalent serovars, such as Salmonella enterica serovar Typhimurium. Live attenuated vaccine strains offer advantages in terms of enhancing cell mediated immunity and allowing inoculation by the oral route. However, main failures of these vaccines are the limited cross-protection achieved against heterologous serovars and interference with serological monitoring for infection. We have recently shown that an attenuated S. Enteritidis strain (ΔXIII) is protective against S. Typhimurium in a murine infection model. ΔXIII strain harbours 13 chromosomal deletions that make it unable to produce the sigma factor RpoS and synthesize cyclic-di-GMP (c-di-GMP). In this study, our objectives were to test the protective effects of ΔXIII strain in swine and to investigate if the use of ΔXIII permits the discrimination of vaccinated from infected pigs. Results show that oral vaccination of pre-weaned piglets with ΔXIII cross-protected against a challenge with S. Typhimurium by reducing faecal shedding and ileocaecal lymph nodes colonization, both at the time of weaning and slaughter. Vaccinated pigs showed neither faecal shedding nor tissue persistence of the vaccine strain at weaning, ensuring the absence of ΔXIII strain by the time of slaughter. Moreover, lack of the SEN4316 protein in ΔXIII strain allowed the development of a serological test that enabled the differentiation of infected from vaccinated animals (DIVA).

scholarly journals Attenuated Salmonella enterica Serovar Typhimurium, Strain NC983, Is Immunogenic, and Protective against Virulent Typhimurium Challenges in Mice

Vaccines ◽  
2020 ◽  
Vol 8 (4) ◽  
pp. 646
Author(s):  
Bryan Troxell ◽  
Mary Mendoza ◽  
Rizwana Ali ◽  
Matthew Koci ◽  
Hosni Hassan
Keyword(s):  
Vaccine Strain ◽  
Oral Delivery ◽  
Salmonella Enterica Serovar Typhimurium ◽  
Live Attenuated Vaccine ◽  
Typhimurium Strain ◽  
Health Burden ◽  
Serovar Typhimurium ◽  
Murine Liver ◽  
Further Development ◽  
Significant Health

Non-typhoidal Salmonella (NTS) serovars are significant health burden worldwide. Although much effort has been devoted to developing typhoid-based vaccines for humans, currently there is no NTS vaccine available. Presented here is the efficacy of a live attenuated serovar Typhimurium strain (NC983). Oral delivery of strain NC983 was capable of fully protecting C57BL/6 and BALB/c mice against challenge with virulent Typhimurium. Strain NC983 was found to elicit an anti-Typhimurium IgG response following administration of vaccine and boosting doses. Furthermore, in competition experiments with virulent S. Typhimurium (ATCC 14028), NC983 was highly defective in colonization of the murine liver and spleen. Collectively, these results indicate that strain NC983 is a potential live attenuated vaccine strain that warrants further development.

scholarly journals The enzyme phosphoglucomutase (Pgm) is required by Salmonella enterica serovar Typhimurium for O-antigen production, resistance to antimicrobial peptides and in vivo fitness

Microbiology ◽  
2009 ◽  
Vol 155 (10) ◽  
pp. 3403-3410 ◽  
Author(s):  
G. K. Paterson ◽  
D. B. Cone ◽  
S. E. Peters ◽  
D. J. Maskell
Keyword(s):  
Antimicrobial Peptides ◽  
Salmonella Enterica ◽  
Salmonella Enterica Serovar Typhimurium ◽  
Live Attenuated Vaccine ◽  
Antigen Production ◽  
O Antigen ◽  
Serovar Typhimurium

The enzyme phosphoglucomutase (Pgm) catalyses the interconversion of glucose 1-phosphate and glucose 6-phosphate and contributes to glycolysis and the generation of sugar nucleotides for biosynthesis. To assess the role of this enzyme in the biology of the pathogen Salmonella enterica serovar Typhimurium we have characterized a pgm deletion mutant in strain SL1344. Compared to SL1344, SL1344 pgm had impaired growth in vitro, was deficient in the ability to utilize galactose as a carbon source and displayed reduced O-antigen polymer length. The mutant was also more susceptible to antimicrobial peptides and showed decreased fitness in the mouse typhoid model. The in vivo phenotype of SL1344 pgm indicated a role for pgm in the early stages of infection, most likely through deficient O-antigen production. Although pgm mutants in other pathogens have potential as live attenuated vaccine strains, SL1344 pgm was not sufficiently attenuated for such use.

scholarly journals Hot Spot for a Large Deletion in the 18- to 19-Centisome Region Confers a Multiple Phenotype in Salmonella enterica Serovar Typhimurium Strain ATCC 14028

2004 ◽  
Vol 186 (24) ◽  
pp. 8516-8523 ◽  
Author(s):  
Sean R. Murray ◽  
Karim Suwwan de Felipe ◽  
Pamela L. Obuchowski ◽  
Jeremy Pike ◽  
David Bermudes ◽  
...  
Keyword(s):  
Salmonella Enterica ◽  
Hot Spot ◽  
Reductase Activity ◽  
Luria Broth ◽  
Large Deletion ◽  
Gas Production ◽  
Strain Atcc ◽  
Wild Type ◽  
Typhimurium Strain ◽  
Serovar Typhimurium

ABSTRACT Loss of the Salmonella MsbB enzyme, which catalyzes the incorporation of myristate destined for lipopolysaccharide in the outer membrane, results in a strong phenotype of sensitivity to salt and chelators such as EGTA and greatly diminished endotoxic activity. MsbB− salmonellae mutate extragenically to EGTA-tolerant derivatives at a frequency of 10−4 per division. One of these derivatives arose from inactivation of somA, which suppresses sensitivity to salt and EGTA. Here we show that a second mode of MsbB− suppression is a RecA-dependent deletion between two IS200 insertion elements present in Salmonella enterica serovar Typhimurium strain ATCC 14028 but not in two other wild-type strains, LT2 and SL1344, which lack one of the IS200 elements. This deletion occurs spontaneously in wild-type and MsbB− strain 14028 salmonellae and accounts for about one-third of all of the spontaneous suppressors of MsbB− in strain 14028. It spans the region corresponding to 17.7 to 19.9 centisomes, which includes somA, on the sequenced map of Salmonella LT2 (136 ORFs in that strain; ATCC 14028 and other strains showed variability in this region). In addition to conferring EGTA resistance correlated with somA, the deletion confers a MacConkey galactose resistance phenotype on MsbB− Salmonella, indicating that at least one additional gene (distinct from somA) within the deletion is responsible for this phenotype. In the wild type, the deletion mutant grows with normal exponential growth rate in Luria broth but is chlorate resistant and does not grow on citrate agar. The deletion strains have lost hydrogen sulfide production, nitrate reductase activity, and gas production from glucose fermentation.

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