PubMed Health⌕ Search

Biomedical subjects

C Hormaeche

Publications and source records attributed to C Hormaeche.

10 recordsLinked to original sources
PubMed1995

The development of oral vaccines against parasitic diseases utilizing live attenuated Salmonella.

Genetically defined, live attenuated Salmonella vaccines are proving useful both as oral vaccines against salmonellosis and for the development of multivalent vaccines based on the expression of heterologous antigens in such strains. Several candidate attenuated S. typhi strains are at present being evaluated as new single dose oral typhoid vaccines in human volunteers. The emergence of such a vaccine will facilitate the development of multivalent vaccines for humans. Many antigens from different infectious organisms have been expressed in attenuated Salmonella. A focus of this work has been on developing vaccines against parasitic diseases. This review will summarize the efforts that have been made in this area.

Administration, Oral↗
PubMed1991

The role of a stress-response protein in Salmonella typhimurium virulence.

We recently described the use of selective transposon mutagenesis to generate a series of avirulent mutants of a pathogenic strain of Salmonella typhimurium. Cloning and sequencing of the insertion sites from two of these mutants reveals that both have identical locations within an open reading frame that is highly homologous to a gene, htrA, encoding a heat-shock protein in Escherichia coli. DNA sequence analysis of S. typhimurium htrA reveals the presence of a gene capable of encoding a protein with a calculated Mr of 49316 that has 88.7% protein:protein homology with its E. coli counterpart. In E. coli, lesions in this gene, also known as degP, reduce proteolytic degradation of aberrant periplasmic proteins. Characteristics of the S. typhimurium htrA mutants, 046 and 014, in vivo and in vitro suggested that they are avirulent because of impaired ability to survive and/or replicate in host tissues. In vitro, the S. typhimurium htrA mutants 046 and 014 are not temperature-sensitive but were found to be more susceptible to oxidative stress than the parent, suggesting that they may be less able to withstand oxidative killing within macrophages.

Alkaline Phosphatase↗
PubMed1990

Yersinia enterocolitica aroA mutants as carriers of the B subunit of the Escherichia coli heat-labile enterotoxin to the murine immune system.

Plasmid p5F which directs the expression of the Escherichia coli heat-labile enterotoxin B subunit (LT-B) from the ptac promoter was introduced into the attenuated Yersinia enterocolitica O:8 aroA mutant strain YAM.1. YAM.1 (p5F) expressed high levels of cell-associated and secreted LT-B in a stable fashion when grown on normal laboratory medium. The strain was used as a live oral vaccine in BALB/c mice and vaccinated mice developed high levels of gut-associated and systemic antibodies to both LT-B and the lipopolysaccharide (LPS) of the vaccine strain. Anti-LT-B and anti-LPS responses in the sera were predominantly of the IgG class whereas gut-associated antibodies were predominantly IgA. ELISPOT assays carried out on selected tissues prepared from vaccinated mice showed significant numbers of cells synthesising IgG and IgA antibodies to LT-B. These results show that Y. enterocolitica aroA mutants can be used effectively as carriers of heterologous antigens to the murine immune system.

Animals↗
PubMed1989

Bacteriophage P22 as a vehicle for transducing cosmid gene banks between smooth strains of Salmonella typhimurium: use in identifying a role for aroD in attenuating virulent Salmonella strains.

A cosmid gene bank of the virulent Salmonella typhimurium C5 was constructed in Escherichia coli K12. The bank was repackaged into bacteriophage heads and transduced into the semi-rough S. typhimurium strain AS68 which expresses the LamB lambda receptor protein. Approximately 6000 ampicillin-resistant transductants were pooled and used as host for the propagation of bacteriophage P22. The P22 lysate was able to transduce cosmid recombinants to smooth strains of S. typhimurium and individual transductants were selected which complemented various S. typhimurium auxotrophic mutations. A stable mutation was introduced into the aroD gene of S. typhimurium C5. The resulting aroD- mutant, named CU038, was highly attenuated compared with the wild-type parent strain and BALB/c mice immunised orally with CU038 were well protected against challenge with the virulent C5 parental strain. Using the cosmid bank repackaged into bacteriophage P22 heads it was possible to isolate cosmid recombinants that could complement the aroD mutation of CU038 either by in vitro selection using minimal medium or in vivo selection for restoration of virulence in BALB/c mice. Repackaged P22 cosmid banks could provide a simple system for selecting in vivo for Salmonella virulence determinants. A Salmonella typhi strain harbouring mutations in aroA and aroD was constructed for potential use as a live oral typhoid vaccine in humans.

Animals↗
PubMed1989

Isolation of orally attenuated Salmonella typhimurium following TnphoA mutagenesis.

One hundred fifty Tn5 IS50L::phoA (TnphoA) mutants of a mouse-virulent, nalidixic acid-resistant (Nalr), prototrophic Salmonella typhimurium strain, C5 Nalr, were isolated. None of the mutants were auxotrophs. Groups of 8 to 10 BALB/c mice were infected orally with each of 95 mutants with a dose equivalent to 20-fold the 50% lethal dose of the wild-type C5 Nalr strain, and deaths were counted over the next 28 days. Fifteen of the mutants failed to kill any mice, whereas all mice died following challenge with the other mutants. Nine of the 15 attenuated mutants exhibited a defect in lipopolysaccharide biosynthesis. The remaining six mutants were smooth. The TnphoA transposon of each of the smooth attenuated mutants was moved, using P22-mediated transduction, into a fresh C5 background, and all retransductants were still attenuated. Analysis of the membrane proteins of the attenuated mutants failed to reveal any alterations in detectable major outer membrane proteins, although colonies of two of the mutants exhibited a mucoid phenotype following growth on L-agar plates. Individual attenuated mutants differed in their abilities to translocate to livers and spleens of mice following oral infection. All of the smooth TnphoA mutants exhibited increased 50% lethal doses with respect to the wild type following intravenous infection of BALB/c mice. Southern analysis of DNA prepared from each of the mutants suggested that TnphoA had inserted into a number of different sites in the S. typhimurium genome. None of the TnphoA mutants had inserts in the virulence-associated plasmid.

Administration, Oral↗
PubMed1988

Oral vaccination.

Explore the source record for details and available documents.

Administration, Oral↗
PubMed1987

Isolation of stable aroA mutants of Salmonella typhi Ty2: properties and preliminary characterisation in mice.

Derivatives of the Salmonella typhi strain Ty2 carrying stable mutations in the aroA gene were isolated. The mutations were generated by transducing an aroA::Tn10 marker into Ty2 and selecting for derivatives which were tetracycline sensitive and dependent on aromatic compounds for growth. Isolates that did not revert to aromatic compound independence at a detectable frequency were obtained. An S. typhimurium derived aroA specific DNA probe was used to demonstrate the presence of DNA rearrangements in the aroA region of the chromosome of some of the S. typhi aroA mutants. Most of these isolates still expressed Vi antigen. Aromatic compound dependent mutants of S. typhi were less virulent in mice than S. typhi Ty2 following intraperitoneal challenge with bacteria suspended in mucin. Mice immunised with one of these mutants, named WBL85-1, were protected against a potentially lethal challenge of S. typhi Ty2.

Animals↗
PubMed1986

In vivo properties of a cloned K88 adherence antigen determinant.

An Escherichia coli strain of serotype O9:K36:H19 harboring the K88 recombinant plasmid pMK005 was able to efficiently colonize the small bowel of young piglets after oral infection. The strain expressed K88 antigen in vivo, and bacteria were detected in close association with the surface of the intestinal villi. Mice infected orally or intravenously with attenuated Salmonella typhimurium SL3261 harboring pMK005 were well protected against subsequent challenge with the highly virulent S. typhimurium SL1344. Anti-K88 antibodies were detected in the serum of mice immunized with SL3261(pMK005).

Adhesins, Escherichia coli↗