G. Dougan

Details der Publikationsliste

Zeitraum

1990 - 2006

Anzahl

125

Co-Autoren

The multidrug-resistant human pathogen clostridium difficile has a highly mobile, mosaic genome (2006)

Sebaihia, M., Wren, B.W., Mullany, P., Fairweather, N.F., Minton, N., Stabler, R., ...

We determined the complete genome sequence of Clostridium difficile strain 630, a virulent and multidrug-resistant strain. Our analysis indicates that a large proportion (11%) of the genome consists...

Universal DNA primers amplify bacterial DNA from human fetal membranes and link Fusobacterium nucleatum with prolonged preterm membrane rupture (2005)

Cahill, R.J., Tan, S., Dougan, G., O’Gaora, P., Pickard, D., Kennea, N., ...

A large number of bacterial species have been identified in fetal membranes after preterm labour (PTL) associated with intrauterine infection by microbiological culture. In this study, we have...

Universal DNA primers amplify bacterial DNA from human fetal membranes and link Fusobacterium nucleatum with prolonged preterm membrane rupture (2005)

Cahill, R.J., Tan, S., Dougan, G., O’Gaora, P., Pickard, D., Kennea, N., ...

A large number of bacterial species have been identified in fetal membranes after preterm labour (PTL) associated with intrauterine infection by microbiological culture. In this study, we have...

Distribution of the saa gene in strains of Shiga toxin-producing Escherichia coli of human and bovine origins (2003)

Jenkins, C., Perry, N. T., Cheasty, T., Shaw, D. J., Frankel, G., Dougan, G., ...

Certain strains of Shiga toxin-producing Escherichia coli (STEC) which do not have the locus of enterocyte effacement pathogenicity island carry the STEC autoagglutinating adhesin (saa) gene. The...

Distribution of the saa gene in strains of Shiga toxin-producing Escherichia coli of human and bovine origins (2003)

Jenkins, C., Perry, N. T., Cheasty, T., Shaw, D. J., Frankel, G., Dougan, G., ...

Certain strains of Shiga toxin-producing Escherichia coli (STEC) which do not have the locus of enterocyte effacement pathogenicity island carry the STEC autoagglutinating adhesin (saa) gene. The...

Refocusing of B-cell responses following a single amino acid substitution in an antigen (2001)

Chiesa, M.D., Martensen, P.M., Simmons, C., Porakishvili, N., Justensen, J., Dougan, G., ...

Intranasal immunization of BALB/c strain mice was carried out using baculovirus-derived human chorionic gonadotrophin (hCG) β-chain, together with Escherichia coli heat-labile enterotoxin....

Differences in the effectiveness of delivery of B- and CTL-epitopes incorporated into the Hepatitis B core antigen (HBcAg) c/e1-region (1999)

Street, M., Herd, K., Londono, P., Doan, T., Dougan, G., Kast, W. M., ...

Work from a number of laboratories including our own has shown that foreign B-epitopes inserted into the c/e1-region of Hepatitis B core antigen (HBcAg) elicit powerful-antibody responses when mice...

Differences in the effectiveness of delivery of B- and CTL-epitopes incorporated into the Hepatitis B core antigen (HBcAg) c/e1-region (1999)

Street, M., Herd, K., Londono, P., Doan, T., Dougan, G., Kast, W. M., ...

Work from a number of laboratories including our own has shown that foreign B-epitopes inserted into the c/e1-region of Hepatitis B core antigen (HBcAg) elicit powerful-antibody responses when mice...

Mutants of Escherichia coli heat-labile toxin lacking ADP-ribosyltransferase activity act as nontoxic, mucosal adjuvants.

Douce, G, Turcotte, C, Cropley, I, Roberts, M, Pizza, M, Domenghini, M, ...

A nontoxic mutant (LTK7) of the Escherichia coli heat-labile enterotoxin (LT) lacking ADP-ribosylating activity but retaining holotoxin formation was constructed. By using site-directed mutagenesis,...

Interleukin 18 Contributes to Host Resistance and Gamma Interferon Production in Mice Infected with Virulent Salmonella typhimurium

Mastroeni, Pietro, Clare, S., Khan, S., Harrison, J. A., Hormaeche, C. E., Okamura, H., ...

Spleen and peritoneal macrophages obtained from innately resistant A/J mice released low levels of interleukin 18 (IL-18) upon infection with Salmonella typhimurium C5 RP4. Incubating the cells with...

Igh-6−/− (B-Cell-Deficient) Mice Fail To Mount Solid Acquired Resistance to Oral Challenge with Virulent Salmonella enterica Serovar Typhimurium and Show Impaired Th1 T-Cell Responses to Salmonella Antigens

Mastroeni, Pietro, Simmons, C., Fowler, R., Hormaeche, C. E., Dougan, G.

In the present study we evaluated the role of B cells in acquired immunity to Salmonella infection by using gene-targeted B-cell-deficient innately susceptible mice on a C57BL/6 background...

Characterization of an Isogenic Mutant of Streptococcus pyogenes Manfredo Lacking the Ability To Make Streptococcal Acid Glycoprotein

Degnan, B. A., Fontaine, M. C., Doebereiner, A. H., Lee, J. J., Mastroeni, P., Dougan, G., ...

An isogenic mutant of Streptococcus pyogenes Manfredo that lacks the ability to make streptococcal acid glycoprotein (SAGP) has been constructed by inserting a deletion in the sagp gene using the...

Interleukin-12 Is Required for Control of the Growth of Attenuated Aromatic-Compound-Dependent Salmonellae in BALB/c Mice: Role of Gamma Interferon and Macrophage Activation

Mastroeni, Pietro, Harrison, J. A., Robinson, J. H., Clare, S., Khan, S., Maskell, D. J., ...

The attenuated S. typhimurium SL3261 (aroA) strain causes mild infections in BALB/c mice. We were able to exacerbate the disease by administering anti-interleukin-12 (IL-12) antibodies, resulting in...

A Mutant of Burkholderia pseudomallei, Auxotrophic in the Branched Chain Amino Acid Biosynthetic Pathway, Is Attenuated and Protective in a Murine Model of Melioidosis

Atkins, T., Prior, R. G., Mack, K., Russell, P., Nelson, M., Oyston, P. C. F., ...

Using a transposon mutagenesis approach, we have identified a mutant of Burkholderia pseudomallei that is auxotrophic for branched chain amino acids. The transposon was shown to have interrupted the...

Biological and genetic characterization of TnphoA mutants of Salmonella typhimurium TML in the context of gastroenteritis.

Lodge, J, Douce, G R, Amin, I I, Bolton, A J, Martin, G D, Chatfield, S, ...

TnphoA transposon insertion mutants of phoN-negative derivatives of Salmonella typhimurium TML (of human gastroenteritic origin) were selected by growing mutagenized recipient bacteria under a...

A mutant pertussis toxin molecule that lacks ADP-ribosyltransferase activity, PT-9K/129G, is an effective mucosal adjuvant for intranasally delivered proteins.

Roberts, M, Bacon, A, Rappuoli, R, Pizza, M, Cropley, I, Douce, G, ...

We examined the capacity of a genetically detoxified derivative of pertussis toxin (PTX), PT-9K/129G, to act as a mucosal adjuvant for an intranasally (i.n.) administered tetanus vaccine. Groups of...

Characterization of recombinant tetanus toxin derivatives suitable for vaccine development.

Figueiredo, D, Turcotte, C, Frankel, G, Li, Y, Dolly, O, Wilkin, G, ...

Recombinant derivatives of tetanus toxin (TeTx) were isolated and used to immunize mice. Recombinant TeTx light chain, a derivative of fragment C that had lost the ability to bind neurons, and a...

Molecular characterization of a carboxy-terminal eukaryotic-cell-binding domain of intimin from enteropathogenic Escherichia coli.

Frankel, G, Candy, D C, Fabiani, E, Adu-Bobie, J, Gil, S, Novakova, M, ...

A eukaryotic cell-binding domain from the intimin (Int) polypeptide of enteropathogenic Escherichia coli O127 (EPEC) was investigated. Derivatives of the carboxy-terminal 280-amino-acid domains of...

Induction of antigen-specific antibodies in vaginal secretions by using a nontoxic mutant of heat-labile enterotoxin as a mucosal adjuvant.

Di Tommaso, A, Saletti, G, Pizza, M, Rappuoli, R, Dougan, G, Abrignani, S, ...

Immunization of the female reproductive tract is important for protection against sexually transmitted diseases and other pathogens of the reproductive tract. However, intravaginal immunization with...

Construction and characterization of a Yersinia enterocolitica O:8 high-temperature requirement (htrA) isogenic mutant.

Li, S R, Dorrell, N, Everest, P H, Dougan, G, Wren, B W

The high-temperature requirement (HtrA) family of stress response proteins are induced by different environmental stress conditions in a variety of bacteria and have been shown to contribute to the...

Immune response in mice following immunization with DNA encoding fragment C of tetanus toxin.

Anderson, R, Gao, X M, Papakonstantinopoulou, A, Roberts, M, Dougan, G

Tetanus toxin is a potent neurotoxin synthesized by Clostridium tetani. Immunization with fragment C protein, the nontoxic C-terminal domain of tetanus toxin, will protect mice against lethal...

Intimin from enteropathogenic Escherichia coli restores murine virulence to a Citrobacter rodentium eaeA mutant: induction of an immunoglobulin A response to intimin and EspB.

Frankel, G, Phillips, A D, Novakova, M, Field, H, Candy, D C, Schauer, D B, ...

The formation of attaching and effacing (A/E) lesions is central to the pathogenesis of enteropathogenic Escherichia coli (EPEC)-mediated disease in humans and Citrobacter rodentium (formerly C....

Safety of live oral Salmonella typhi vaccine strains with deletions in htrA and aroC aroD and immune response in humans.

Tacket, C O, Sztein, M B, Losonsky, G A, Wasserman, S S, Nataro, J P, Edelman, R, ...

A single-dose, oral Salmonella typhi vaccine strain has been sought as a carrier or vector of cloned genes encoding protective antigens of other pathogens. Such a hybrid vaccine, administered orally,...

Down regulation of intimin expression during attaching and effacing enteropathogenic Escherichia coli adhesion.

Knutton, S, Adu-Bobie, J, Bain, C, Phillips, A D, Dougan, G, Frankel, G

Enteropathogenic Escherichia coli (EPEC) produces attaching and effacing (A/E) lesions in the intestinal mucosa. The intimate bacterial adhesion associated with A/E lesion formation is promoted by...

Intranasal immunogenicity and adjuvanticity of site-directed mutant derivatives of cholera toxin.

Douce, G, Fontana, M, Pizza, M, Rappuoli, R, Dougan, G

Genetically modified derivatives of cholera toxin (CT), harboring a single amino acid substitution in and around the NAD binding cleft of the A subunit, were isolated following site-directed...

Influence of genes encoding proton-translocating enzymes on suppression of Salmonella typhimurium growth and colonization.

Zhang-Barber, L, Turner, A K, Martin, G, Frankel, G, Dougan, G, Barrow, P A

Twenty-four-hour-old, aerobically grown, Luria-Bertani broth cultures of Salmonella typhimurium F98 suppressed the growth of a spectinomycin-resistant (Spcr) derivative of the same strain inoculated...

Characterization of the C-terminal domains of intimin-like proteins of enteropathogenic and enterohemorrhagic Escherichia coli, Citrobacter freundii, and Hafnia alvei.

Frankel, G, Candy, D C, Everest, P, Dougan, G

Surface proteins called intimins (Int), which are homologous to the invasin protein (Inv) of Yersinia spp., play a role in inducing brush border damage, termed attachment and effacement, which...

Chimeric hepatitis B virus core particles as probes for studying peptide-integrin interactions.

Chambers, M A, Dougan, G, Newman, J, Brown, F, Crowther, J, Mould, A P, ...

An RGD-containing epitope from the foot-and-mouth disease virus (FMDV) VP1 protein was inserted into the e1 loop of the hepatitis B virus core (HBc) protein. This chimeric protein was expressed at...

Cloning and characterization of the aroA gene from Mycobacterium tuberculosis.

Garbe, T, Jones, C, Charles, I, Dougan, G, Young, D

The aroA gene from Mycobacterium tuberculosis has been cloned by complementation of an aroA mutant of Escherichia coli after lysogenization with a recombinant DNA library in the lambda gt11 vector....

Cloning and nucleotide sequence of the aroA gene of Bordetella pertussis.

Maskell, D J, Morrissey, P, Dougan, G

The aroA locus of Bordetella pertussis, encoding 5-enolpyruvylshikimate 3-phosphate synthase, has been cloned into Escherichia coli by using a cosmid vector. The gene is expressed in E. coli and...

Cloning of chromosomal DNA encoding the F41 adhesin of enterotoxigenic Escherichia coli and genetic homology between adhesins F41 and K88.

Moseley, S L, Dougan, G, Schneider, R A, Moon, H W

The genetic determinant for production of the adhesive antigen F41 was isolated from a porcine enterotoxigenic Escherichia coli strain by cosmid cloning. The cloned DNA included sequences homologous...

Identification and cloning of the genetic determinant that encodes for the K88ac adherence antigen.

Shipley, P L, Dougan, G, Falkow, S

Strains of Escherichia coli capable of causing diarrhea in young pigs are often able to proliferate in the upper small intestine of the infected animal due to the presence of a specific surface...

Organization of K88ac-encoded polypeptides in the Escherichia coli cell envelope: use of minicells and outer membrane protein mutants for studying assembly of pili.

Dougan, G, Dowd, G, Kehoe, M

Escherichia coli K-12 minicells, harboring recombinant plasmids encoding polypeptides involved in the expression of K88ac adhesion pili on the bacterial cell surface, were labeled with...

Polypeptides expressed in Escherichia coli K-12 minicells by transposition elements Tn1 and Tn3.

Dougan, G, Saul, M, Twigg, A, Gill, R, Sherratt, D

Escherichia coli K-12 minicells were employed to examine polypeptides encoded by plasmids carrying wild-type and mutant Tn1 or Tn3 transposition elements. Tn1- and Tn3-containing minicells express...

Analysis of sequences transposed by complementation of two classes of transposition-deficient mutants of Tn3.

Gill, R, Heffron, F, Dougan, G, Falkow, S

The Tn1 and Tn3 elements are closely related transposons which carry the structural gene for ampicillin resistance. Two classes of deletion mutants of the plasmid pMB8::Tn3 (RSF1050) are unable to...

Cloning, and expression in Escherichia coli K-12, of the chromosomal hemolysin (phospholipase C) determinant of Pseudomonas aeruginosa.

Coleman, K, Dougan, G, Arbuthnott, J P

A hemolysin determinant was cloned from Pseudomonas aeruginosa PA103 by inserting Sau3a-generated DNA fragments between the BamHI sites of the lambda replacement vector WL47.1. A 9.5-kilobase HindIII...

Changes in protein synthesis on mitomycin C induction of wild-type and mutant CloDF13 plasmids.

Dougan, G, Sherratt, D J

Mitomycin C treatment of Escherichia coli K-12 cells containing the nonconjugative plasmid CloDF13 resulted in inhibition of host chromosome protein synthesis and a high rate of synthesis of two...

Identification of T- and B-cell epitopes of the E7 protein of human papillomavirus type 16.

Comerford, S A, McCance, D J, Dougan, G, Tite, J P

There is strong evidence implicating human papillomavirus type 16 (HPV16) in the genesis of human genital cancer. Viral DNA has been identified in invasive carcinoma of the uterine cervix and in cell...

Characterization of a Salmonella typhimurium aro vaccine strain expressing the P.69 antigen of Bordetella pertussis.

Strugnell, R, Dougan, G, Chatfield, S, Charles, I, Fairweather, N, Tite, J, ...

The P.69 Bordetella pertussis protective antigen was expressed by use of the trc promoter from the chromosome of a Salmonella typhimurium aro vaccine strain, BRD509, by integrating the prn gene,...

Role of ompR-dependent genes in Salmonella typhimurium virulence: mutants deficient in both ompC and ompF are attenuated in vivo.

Chatfield, S N, Dorman, C J, Hayward, C, Dougan, G

A Salmonella typhimurium strain harboring stable mutations in both ompC and ompF was constructed from the mouse-virulent strain S. typhimurium SL1344. When administered orally to BALB/c mice the...

Construction and characterization in vivo of Bordetella pertussis aroA mutants.

Roberts, M, Maskell, D, Novotny, P, Dougan, G

A DNA fragment encoding a kanamycin resistance determinant was used to insertionally inactivate the cloned aroA gene of Bordetella pertussis in Escherichia coli K-12, and a conjugative shuttle vector...

Oral vaccination of mice against tetanus by use of a live attenuated Salmonella carrier.

Fairweather, N F, Chatfield, S N, Makoff, A J, Strugnell, R A, Bester, J, Maskell, D J, ...

A Salmonella typhimurium aroA mutant has been used as a live carrier to immunize mice against tetanus. Plasmid pTETtac4, which expresses a 50-kilodalton fragment of tetanus toxin (fragment C) under...

Characterization of aromatic- and purine-dependent Salmonella typhimurium: attention, persistence, and ability to induce protective immunity in BALB/c mice.

O'Callaghan, D, Maskell, D, Liew, F Y, Easmon, C S, Dougan, G

Stable transposon-generated auxotrophic mutations in aroA, purA, and purE or aroA and purA together were introduced into Salmonella typhimurium strains which were virulent in mice. Strains harboring...

Identification of the major antigens of Treponema hyodysenteriae and comparison with those of Treponema innocens.

Chatfield, S N, Fernie, D S, Penn, C, Dougan, G

Eleven strains of Treponema hyodysenteriae isolated from pigs with swine dysentery were examined by using sodium dodecyl sulfate-polyacrylamide gel electrophoresis and immunoblotting. T....

Virulence, persistence, and immunogenicity of Yersinia enterocolitica O:8 aroA mutants.

Bowe, F, O'Gaora, P, Maskell, D, Cafferkey, M, Dougan, G

The virulent Yersinia enterocolitica strain 8081 killed BALB/c mice within 5 days of oral infection with a 50% lethal dose of log10 7.1, whereas an aroA mutant of 8081, YAM.1, and the plasmidless...

In vivo properties of a cloned K88 adherence antigen determinant.

Dougan, G, Sellwood, R, Maskell, D, Sweeney, K, Liew, F Y, Beesley, J, ...

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...

Cloning, expression, and mapping of the Staphylococcus aureus alpha-hemolysin determinant in Escherichia coli K-12.

Kehoe, M, Duncan, J, Foster, T, Fairweather, N, Dougan, G

A fragment of Staphylococcus aureus DNA encoding the alpha-hemolysin determinant was cloned from strain Wood 46 by inserting Sau3A-generated genomic DNA fragments between the BamHI sites of the...

Expression of a cloned Staphylococcus aureus alpha-hemolysin determinant in Bacillus subtilis and Staphylococcus aureus.

Fairweather, N, Kennedy, S, Foster, T J, Kehoe, M, Dougan, G

A DNA sequence encoding Staphylococcus aureus alpha-hemolysin, which had been previously cloned and mapped in Escherichia coli K-12, was introduced into Bacillus subtilis BD170 and several strains of...

Antibiotic resistance in Providencia stuartii isolated in hospitals.

McHale, P J, Keane, C T, Dougan, G

A total of 238 isolates of Providencia stuartii obtained from infected patients in six Dublin hospitals were grouped by using serological and bacteriocin typing methods and tested for sensitivity to...

Molecular cloning and characterization of protective outer membrane protein P.69 from Bordetella pertussis.

Charles, I G, Dougan, G, Pickard, D, Chatfield, S, Smith, M, Novotny, P, ...

Protein P.69 is localized on the outer membrane of Bordetella pertussis and is one of the virulence factors believed to contribute to the disease state of whooping cough. We demonstrate that protein...

Characterization of defined ompR mutants of Salmonella typhi: ompR is involved in the regulation of Vi polysaccharide expression.

Pickard, D, Li, J, Roberts, M, Maskell, D, Hone, D, Levine, M, ...

The ompB operon, comprising the ompR and envZ genes, was cloned from a Salmonella typhi Ty2 cosmid bank and characterized by DNA sequence analysis. The S. typhi ompR and envZ genes contained open...

Isolation of orally attenuated Salmonella typhimurium following TnphoA mutagenesis.

Miller, I, Maskell, D, Hormaeche, C, Johnson, K, Pickard, D, Dougan, G

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...

Characterization of porin and ompR mutants of a virulent strain of Salmonella typhimurium: ompR mutants are attenuated in vivo.

Dorman, C J, Chatfield, S, Higgins, C F, Hayward, C, Dougan, G

The ompC, ompD, and ompF genes encode the three major porins of Salmonella typhimurium. ompR encodes a positive regulator required for the expression of ompC and ompF. Transposon-generated mutations...

Shedding Patterns of Verocytotoxin-Producing Escherichia coli Strains in a Cohort of Calves and Their Dams on a Scottish Beef Farm

Shaw, D. J., Jenkins, C., Pearce, M. C., Cheasty, T., Gunn, G. J., Dougan, G., ...

Rectal fecal samples were taken once a week from 49 calves on the same farm. In addition, the dams of the calves were sampled at the time of calf birth and at the end of the study. Strains of...

Inducible overproduction of the Aspergillus nidulans pentafunctional AROM protein and the type-I and -II 3-dehydroquinases from Salmonella typhi and Mycobacterium tuberculosis.

Moore, J D, Lamb, H K, Garbe, T, Servos, S, Dougan, G, Charles, I G, ...

The aroQ gene of Mycobacterium tuberculosis, encoding a type-II 3-dehydroquinase, and the aroD gene of Salmonella typhi, encoding a type-I 3-dehydroquinase, have been highly overexpressed in...

A novel EspA-associated surface organelle of enteropathogenic Escherichia coli involved in protein translocation into epithelial cells.

Knutton, S, Rosenshine, I, Pallen, M J, Nisan, I, Neves, B C, Bain, C, ...

Enteropathogenic Escherichia coli (EPEC), like many bacterial pathogens, employ a type III secretion system to deliver effector proteins across the bacterial cell. In EPEC, four proteins are known to...

Expression of a cloned K88ac adhesion antigen determinant: identification of a new adhesion cistron and role of a vector-encoded promoter.

Kehoe, M, Winther, M, Dougan, G

The determinant for the K88ac adherence antigen of porcine enterotoxigenic Escherichia coli has been cloned previously onto the vector plasmid pBR322 to form the K88ac-pBR322 hybrid plasmid pMK005...

Mutants of Escherichia coli heat-labile toxin lacking ADP-ribosyltransferase activity act as nontoxic, mucosal adjuvants.

Douce, G, Turcotte, C, Cropley, I, Roberts, M, Pizza, M, Domenghini, M, ...

A nontoxic mutant (LTK7) of the Escherichia coli heat-labile enterotoxin (LT) lacking ADP-ribosylating activity but retaining holotoxin formation was constructed. By using site-directed mutagenesis,...

Interleukin 18 Contributes to Host Resistance and Gamma Interferon Production in Mice Infected with Virulent Salmonella typhimurium

Mastroeni, Pietro, Clare, S., Khan, S., Harrison, J. A., Hormaeche, C. E., Okamura, H., ...

Spleen and peritoneal macrophages obtained from innately resistant A/J mice released low levels of interleukin 18 (IL-18) upon infection with Salmonella typhimurium C5 RP4. Incubating the cells with...

Igh-6−/− (B-Cell-Deficient) Mice Fail To Mount Solid Acquired Resistance to Oral Challenge with Virulent Salmonella enterica Serovar Typhimurium and Show Impaired Th1 T-Cell Responses to Salmonella Antigens

Mastroeni, Pietro, Simmons, C., Fowler, R., Hormaeche, C. E., Dougan, G.

In the present study we evaluated the role of B cells in acquired immunity to Salmonella infection by using gene-targeted B-cell-deficient innately susceptible mice on a C57BL/6 background...

Characterization of an Isogenic Mutant of Streptococcus pyogenes Manfredo Lacking the Ability To Make Streptococcal Acid Glycoprotein

Degnan, B. A., Fontaine, M. C., Doebereiner, A. H., Lee, J. J., Mastroeni, P., Dougan, G., ...

An isogenic mutant of Streptococcus pyogenes Manfredo that lacks the ability to make streptococcal acid glycoprotein (SAGP) has been constructed by inserting a deletion in the sagp gene using the...

Interleukin-12 Is Required for Control of the Growth of Attenuated Aromatic-Compound-Dependent Salmonellae in BALB/c Mice: Role of Gamma Interferon and Macrophage Activation

Mastroeni, Pietro, Harrison, J. A., Robinson, J. H., Clare, S., Khan, S., Maskell, D. J., ...

The attenuated S. typhimurium SL3261 (aroA) strain causes mild infections in BALB/c mice. We were able to exacerbate the disease by administering anti-interleukin-12 (IL-12) antibodies, resulting in...

A Mutant of Burkholderia pseudomallei, Auxotrophic in the Branched Chain Amino Acid Biosynthetic Pathway, Is Attenuated and Protective in a Murine Model of Melioidosis

Atkins, T., Prior, R. G., Mack, K., Russell, P., Nelson, M., Oyston, P. C. F., ...

Using a transposon mutagenesis approach, we have identified a mutant of Burkholderia pseudomallei that is auxotrophic for branched chain amino acids. The transposon was shown to have interrupted the...

Biological and genetic characterization of TnphoA mutants of Salmonella typhimurium TML in the context of gastroenteritis.

Lodge, J, Douce, G R, Amin, I I, Bolton, A J, Martin, G D, Chatfield, S, ...

TnphoA transposon insertion mutants of phoN-negative derivatives of Salmonella typhimurium TML (of human gastroenteritic origin) were selected by growing mutagenized recipient bacteria under a...

A mutant pertussis toxin molecule that lacks ADP-ribosyltransferase activity, PT-9K/129G, is an effective mucosal adjuvant for intranasally delivered proteins.

Roberts, M, Bacon, A, Rappuoli, R, Pizza, M, Cropley, I, Douce, G, ...

We examined the capacity of a genetically detoxified derivative of pertussis toxin (PTX), PT-9K/129G, to act as a mucosal adjuvant for an intranasally (i.n.) administered tetanus vaccine. Groups of...

Characterization of recombinant tetanus toxin derivatives suitable for vaccine development.

Figueiredo, D, Turcotte, C, Frankel, G, Li, Y, Dolly, O, Wilkin, G, ...

Recombinant derivatives of tetanus toxin (TeTx) were isolated and used to immunize mice. Recombinant TeTx light chain, a derivative of fragment C that had lost the ability to bind neurons, and a...

Molecular characterization of a carboxy-terminal eukaryotic-cell-binding domain of intimin from enteropathogenic Escherichia coli.

Frankel, G, Candy, D C, Fabiani, E, Adu-Bobie, J, Gil, S, Novakova, M, ...

A eukaryotic cell-binding domain from the intimin (Int) polypeptide of enteropathogenic Escherichia coli O127 (EPEC) was investigated. Derivatives of the carboxy-terminal 280-amino-acid domains of...

Induction of antigen-specific antibodies in vaginal secretions by using a nontoxic mutant of heat-labile enterotoxin as a mucosal adjuvant.

Di Tommaso, A, Saletti, G, Pizza, M, Rappuoli, R, Dougan, G, Abrignani, S, ...

Immunization of the female reproductive tract is important for protection against sexually transmitted diseases and other pathogens of the reproductive tract. However, intravaginal immunization with...

Construction and characterization of a Yersinia enterocolitica O:8 high-temperature requirement (htrA) isogenic mutant.

Li, S R, Dorrell, N, Everest, P H, Dougan, G, Wren, B W

The high-temperature requirement (HtrA) family of stress response proteins are induced by different environmental stress conditions in a variety of bacteria and have been shown to contribute to the...

Immune response in mice following immunization with DNA encoding fragment C of tetanus toxin.

Anderson, R, Gao, X M, Papakonstantinopoulou, A, Roberts, M, Dougan, G

Tetanus toxin is a potent neurotoxin synthesized by Clostridium tetani. Immunization with fragment C protein, the nontoxic C-terminal domain of tetanus toxin, will protect mice against lethal...

Intimin from enteropathogenic Escherichia coli restores murine virulence to a Citrobacter rodentium eaeA mutant: induction of an immunoglobulin A response to intimin and EspB.

Frankel, G, Phillips, A D, Novakova, M, Field, H, Candy, D C, Schauer, D B, ...

The formation of attaching and effacing (A/E) lesions is central to the pathogenesis of enteropathogenic Escherichia coli (EPEC)-mediated disease in humans and Citrobacter rodentium (formerly C....

Safety of live oral Salmonella typhi vaccine strains with deletions in htrA and aroC aroD and immune response in humans.

Tacket, C O, Sztein, M B, Losonsky, G A, Wasserman, S S, Nataro, J P, Edelman, R, ...

A single-dose, oral Salmonella typhi vaccine strain has been sought as a carrier or vector of cloned genes encoding protective antigens of other pathogens. Such a hybrid vaccine, administered orally,...

Down regulation of intimin expression during attaching and effacing enteropathogenic Escherichia coli adhesion.

Knutton, S, Adu-Bobie, J, Bain, C, Phillips, A D, Dougan, G, Frankel, G

Enteropathogenic Escherichia coli (EPEC) produces attaching and effacing (A/E) lesions in the intestinal mucosa. The intimate bacterial adhesion associated with A/E lesion formation is promoted by...

Intranasal immunogenicity and adjuvanticity of site-directed mutant derivatives of cholera toxin.

Douce, G, Fontana, M, Pizza, M, Rappuoli, R, Dougan, G

Genetically modified derivatives of cholera toxin (CT), harboring a single amino acid substitution in and around the NAD binding cleft of the A subunit, were isolated following site-directed...

Influence of genes encoding proton-translocating enzymes on suppression of Salmonella typhimurium growth and colonization.

Zhang-Barber, L, Turner, A K, Martin, G, Frankel, G, Dougan, G, Barrow, P A

Twenty-four-hour-old, aerobically grown, Luria-Bertani broth cultures of Salmonella typhimurium F98 suppressed the growth of a spectinomycin-resistant (Spcr) derivative of the same strain inoculated...

Characterization of the C-terminal domains of intimin-like proteins of enteropathogenic and enterohemorrhagic Escherichia coli, Citrobacter freundii, and Hafnia alvei.

Frankel, G, Candy, D C, Everest, P, Dougan, G

Surface proteins called intimins (Int), which are homologous to the invasin protein (Inv) of Yersinia spp., play a role in inducing brush border damage, termed attachment and effacement, which...

Chimeric hepatitis B virus core particles as probes for studying peptide-integrin interactions.

Chambers, M A, Dougan, G, Newman, J, Brown, F, Crowther, J, Mould, A P, ...

An RGD-containing epitope from the foot-and-mouth disease virus (FMDV) VP1 protein was inserted into the e1 loop of the hepatitis B virus core (HBc) protein. This chimeric protein was expressed at...

Cloning and characterization of the aroA gene from Mycobacterium tuberculosis.

Garbe, T, Jones, C, Charles, I, Dougan, G, Young, D

The aroA gene from Mycobacterium tuberculosis has been cloned by complementation of an aroA mutant of Escherichia coli after lysogenization with a recombinant DNA library in the lambda gt11 vector....

Cloning and nucleotide sequence of the aroA gene of Bordetella pertussis.

Maskell, D J, Morrissey, P, Dougan, G

The aroA locus of Bordetella pertussis, encoding 5-enolpyruvylshikimate 3-phosphate synthase, has been cloned into Escherichia coli by using a cosmid vector. The gene is expressed in E. coli and...

Cloning of chromosomal DNA encoding the F41 adhesin of enterotoxigenic Escherichia coli and genetic homology between adhesins F41 and K88.

Moseley, S L, Dougan, G, Schneider, R A, Moon, H W

The genetic determinant for production of the adhesive antigen F41 was isolated from a porcine enterotoxigenic Escherichia coli strain by cosmid cloning. The cloned DNA included sequences homologous...

Identification and cloning of the genetic determinant that encodes for the K88ac adherence antigen.

Shipley, P L, Dougan, G, Falkow, S

Strains of Escherichia coli capable of causing diarrhea in young pigs are often able to proliferate in the upper small intestine of the infected animal due to the presence of a specific surface...

Organization of K88ac-encoded polypeptides in the Escherichia coli cell envelope: use of minicells and outer membrane protein mutants for studying assembly of pili.

Dougan, G, Dowd, G, Kehoe, M

Escherichia coli K-12 minicells, harboring recombinant plasmids encoding polypeptides involved in the expression of K88ac adhesion pili on the bacterial cell surface, were labeled with...

Expression of a cloned K88ac adhesion antigen determinant: identification of a new adhesion cistron and role of a vector-encoded promoter.

Kehoe, M, Winther, M, Dougan, G

The determinant for the K88ac adherence antigen of porcine enterotoxigenic Escherichia coli has been cloned previously onto the vector plasmid pBR322 to form the K88ac-pBR322 hybrid plasmid pMK005...

Polypeptides expressed in Escherichia coli K-12 minicells by transposition elements Tn1 and Tn3.

Dougan, G, Saul, M, Twigg, A, Gill, R, Sherratt, D

Escherichia coli K-12 minicells were employed to examine polypeptides encoded by plasmids carrying wild-type and mutant Tn1 or Tn3 transposition elements. Tn1- and Tn3-containing minicells express...

Analysis of sequences transposed by complementation of two classes of transposition-deficient mutants of Tn3.

Gill, R, Heffron, F, Dougan, G, Falkow, S

The Tn1 and Tn3 elements are closely related transposons which carry the structural gene for ampicillin resistance. Two classes of deletion mutants of the plasmid pMB8::Tn3 (RSF1050) are unable to...

Cloning, and expression in Escherichia coli K-12, of the chromosomal hemolysin (phospholipase C) determinant of Pseudomonas aeruginosa.

Coleman, K, Dougan, G, Arbuthnott, J P

A hemolysin determinant was cloned from Pseudomonas aeruginosa PA103 by inserting Sau3a-generated DNA fragments between the BamHI sites of the lambda replacement vector WL47.1. A 9.5-kilobase HindIII...

Changes in protein synthesis on mitomycin C induction of wild-type and mutant CloDF13 plasmids.

Dougan, G, Sherratt, D J

Mitomycin C treatment of Escherichia coli K-12 cells containing the nonconjugative plasmid CloDF13 resulted in inhibition of host chromosome protein synthesis and a high rate of synthesis of two...

Identification of T- and B-cell epitopes of the E7 protein of human papillomavirus type 16.

Comerford, S A, McCance, D J, Dougan, G, Tite, J P

There is strong evidence implicating human papillomavirus type 16 (HPV16) in the genesis of human genital cancer. Viral DNA has been identified in invasive carcinoma of the uterine cervix and in cell...

Characterization of a Salmonella typhimurium aro vaccine strain expressing the P.69 antigen of Bordetella pertussis.

Strugnell, R, Dougan, G, Chatfield, S, Charles, I, Fairweather, N, Tite, J, ...

The P.69 Bordetella pertussis protective antigen was expressed by use of the trc promoter from the chromosome of a Salmonella typhimurium aro vaccine strain, BRD509, by integrating the prn gene,...

Role of ompR-dependent genes in Salmonella typhimurium virulence: mutants deficient in both ompC and ompF are attenuated in vivo.

Chatfield, S N, Dorman, C J, Hayward, C, Dougan, G

A Salmonella typhimurium strain harboring stable mutations in both ompC and ompF was constructed from the mouse-virulent strain S. typhimurium SL1344. When administered orally to BALB/c mice the...

Construction and characterization in vivo of Bordetella pertussis aroA mutants.

Roberts, M, Maskell, D, Novotny, P, Dougan, G

A DNA fragment encoding a kanamycin resistance determinant was used to insertionally inactivate the cloned aroA gene of Bordetella pertussis in Escherichia coli K-12, and a conjugative shuttle vector...

Oral vaccination of mice against tetanus by use of a live attenuated Salmonella carrier.

Fairweather, N F, Chatfield, S N, Makoff, A J, Strugnell, R A, Bester, J, Maskell, D J, ...

A Salmonella typhimurium aroA mutant has been used as a live carrier to immunize mice against tetanus. Plasmid pTETtac4, which expresses a 50-kilodalton fragment of tetanus toxin (fragment C) under...

Characterization of aromatic- and purine-dependent Salmonella typhimurium: attention, persistence, and ability to induce protective immunity in BALB/c mice.

O'Callaghan, D, Maskell, D, Liew, F Y, Easmon, C S, Dougan, G

Stable transposon-generated auxotrophic mutations in aroA, purA, and purE or aroA and purA together were introduced into Salmonella typhimurium strains which were virulent in mice. Strains harboring...

Identification of the major antigens of Treponema hyodysenteriae and comparison with those of Treponema innocens.

Chatfield, S N, Fernie, D S, Penn, C, Dougan, G

Eleven strains of Treponema hyodysenteriae isolated from pigs with swine dysentery were examined by using sodium dodecyl sulfate-polyacrylamide gel electrophoresis and immunoblotting. T....

Virulence, persistence, and immunogenicity of Yersinia enterocolitica O:8 aroA mutants.

Bowe, F, O'Gaora, P, Maskell, D, Cafferkey, M, Dougan, G

The virulent Yersinia enterocolitica strain 8081 killed BALB/c mice within 5 days of oral infection with a 50% lethal dose of log10 7.1, whereas an aroA mutant of 8081, YAM.1, and the plasmidless...

In vivo properties of a cloned K88 adherence antigen determinant.

Dougan, G, Sellwood, R, Maskell, D, Sweeney, K, Liew, F Y, Beesley, J, ...

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...

Cloning, expression, and mapping of the Staphylococcus aureus alpha-hemolysin determinant in Escherichia coli K-12.

Kehoe, M, Duncan, J, Foster, T, Fairweather, N, Dougan, G

A fragment of Staphylococcus aureus DNA encoding the alpha-hemolysin determinant was cloned from strain Wood 46 by inserting Sau3A-generated genomic DNA fragments between the BamHI sites of the...

Expression of a cloned Staphylococcus aureus alpha-hemolysin determinant in Bacillus subtilis and Staphylococcus aureus.

Fairweather, N, Kennedy, S, Foster, T J, Kehoe, M, Dougan, G

A DNA sequence encoding Staphylococcus aureus alpha-hemolysin, which had been previously cloned and mapped in Escherichia coli K-12, was introduced into Bacillus subtilis BD170 and several strains of...

Antibiotic resistance in Providencia stuartii isolated in hospitals.

McHale, P J, Keane, C T, Dougan, G

A total of 238 isolates of Providencia stuartii obtained from infected patients in six Dublin hospitals were grouped by using serological and bacteriocin typing methods and tested for sensitivity to...

Molecular cloning and characterization of protective outer membrane protein P.69 from Bordetella pertussis.

Charles, I G, Dougan, G, Pickard, D, Chatfield, S, Smith, M, Novotny, P, ...

Protein P.69 is localized on the outer membrane of Bordetella pertussis and is one of the virulence factors believed to contribute to the disease state of whooping cough. We demonstrate that protein...

Characterization of defined ompR mutants of Salmonella typhi: ompR is involved in the regulation of Vi polysaccharide expression.

Pickard, D, Li, J, Roberts, M, Maskell, D, Hone, D, Levine, M, ...

The ompB operon, comprising the ompR and envZ genes, was cloned from a Salmonella typhi Ty2 cosmid bank and characterized by DNA sequence analysis. The S. typhi ompR and envZ genes contained open...

Isolation of orally attenuated Salmonella typhimurium following TnphoA mutagenesis.

Miller, I, Maskell, D, Hormaeche, C, Johnson, K, Pickard, D, Dougan, G

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...

Characterization of porin and ompR mutants of a virulent strain of Salmonella typhimurium: ompR mutants are attenuated in vivo.

Dorman, C J, Chatfield, S, Higgins, C F, Hayward, C, Dougan, G

The ompC, ompD, and ompF genes encode the three major porins of Salmonella typhimurium. ompR encodes a positive regulator required for the expression of ompC and ompF. Transposon-generated mutations...

Shedding Patterns of Verocytotoxin-Producing Escherichia coli Strains in a Cohort of Calves and Their Dams on a Scottish Beef Farm

Shaw, D. J., Jenkins, C., Pearce, M. C., Cheasty, T., Gunn, G. J., Dougan, G., ...

Rectal fecal samples were taken once a week from 49 calves on the same farm. In addition, the dams of the calves were sampled at the time of calf birth and at the end of the study. Strains of...

Inducible overproduction of the Aspergillus nidulans pentafunctional AROM protein and the type-I and -II 3-dehydroquinases from Salmonella typhi and Mycobacterium tuberculosis.

Moore, J D, Lamb, H K, Garbe, T, Servos, S, Dougan, G, Charles, I G, ...

The aroQ gene of Mycobacterium tuberculosis, encoding a type-II 3-dehydroquinase, and the aroD gene of Salmonella typhi, encoding a type-I 3-dehydroquinase, have been highly overexpressed in...

A novel EspA-associated surface organelle of enteropathogenic Escherichia coli involved in protein translocation into epithelial cells.

Knutton, S, Rosenshine, I, Pallen, M J, Nisan, I, Neves, B C, Bain, C, ...

Enteropathogenic Escherichia coli (EPEC), like many bacterial pathogens, employ a type III secretion system to deliver effector proteins across the bacterial cell. In EPEC, four proteins are known to...

Protection against Leishmania major infection in genetically susceptible BALB/c mice by gp63 delivered orally in attenuated Salmonella typhimurium (AroA- AroD-).

Xu, D, McSorley, S J, Chatfield, S N, Dougan, G, Liew, F Y

The gene encoding the Leishmania major (L. major) promastigote surface glycoprotein, gp63, was introduced into the Salmonella typhimurium (S. typhimurium) aroA- aroD- live oral vaccine strain BRD509...

Anti-viral immunity induced by recombinant nucleoprotein of influenza A virus. III. Delivery of recombinant nucleoprotein to the immune system using attenuated Salmonella typhimurium as a live carrier.

Tite, J P, Gao, X M, Hughes-Jenkins, C M, Lipscombe, M, O'Callaghan, D, Dougan, G, ...

A plasmid encoding the influenza nucleoprotein gene from A/NT/60/68 virus was transduced into the attenuated Salmonella typhimurium aroA- strain SL3261. The bacterial vector expressing the viral gene...

Anti-viral immunity induced by recombinant nucleoprotein of influenza A virus. II. Protection from influenza infection and mechanism of protection.

Tite, J P, Hughes-Jenkins, C, O'Callaghan, D, Dougan, G, Russell, S M, Gao, X M, ...

Protection against influenza A virus infection in mice immunized with recombinant nucleoprotein (rNP) was studied. Nucleoprotein-immune mice were protected against a lethal challenge with A/Puerto...

Immune responses in BALB/c mice following immunization with aromatic compound or purine-dependent Salmonella typhimurium strains.

O'Callaghan, D, Maskell, D, Tite, J, Dougan, G

Two near isogenic strains of Salmonella typhimurium HWSH, stably mutated in either the aroA gene affecting the biosynthesis of aromatic compounds, or the purA gene affecting the biosynthesis of...

Acquisition of virulence-associated factors by the enteric pathogens Escherichia coli and Salmonella enterica.

Wain, J, House, D, Pickard, D, Dougan, G, Frankel, G

In this review we summarize recent genomic studies that shed light on the mechanism through which pathogenic Escherichia coli and Salmonella enterica have evolved. We show how acquisition of DNA at...

DNA topology and adaptation of Salmonella typhimurium to an intracellular environment.

Marshall, D G, Bowe, F, Hale, C, Dougan, G, Dorman, C J

The expression of genes coding for determinants of DNA topology in the facultative intracellular pathogen Salmonella typhimurium was studied during adaptation by the bacteria to the intracellular...

The immune responses to bacterial antigens encountered in vivo at mucosal surfaces.

Dougan, G, Ghaem-Maghami, M, Pickard, D, Frankel, G, Douce, G, Clare, S, ...

Mammals have evolved a sophisticated immune system for handling antigens encountered at their mucosal surfaces. The way in which mucosally delivered antigens are handled influences our ability to...

Enterohaemorrhagic Escherichia coli O157:H7 target Peyer's patches in humans and cause attaching/effacing lesions in both human and bovine intestine

Phillips, A, Navabpour, S, Hicks, S, Dougan, G, Wallis, T, Frankel, G

BACKGROUND—Enterohaemorrhagic Escherichia coli (EHEC) constitute a significant risk to human health worldwide, and infections, particularly with serogroup O157:H7, are associated with consumption...

Intimin type influences the site of human intestinal mucosal colonisation by enterohaemorrhagic Escherichia coli O157:H7

Fitzhenry, R J, Pickard, D J, Hartland, E L, Reece, S, Dougan, G, Phillips, A D, ...

Background: Enterohaemorrhagic (EHEC) and enteropathogenic (EPEC) Escherichia coli epithelial cell adhesion is characterised by intimate attachment, and attaching and effacing (A/E) lesion formation....

Early interactions of Salmonella enterica serovar typhimurium with human small intestinal epithelial explants

Haque, A, Bowe, F, Fitzhenry, R J, Frankel, G, Thomson, M, Heuschkel, R, ...

Background: Salmonella enterica serovar typhimurium (Styphimurium) causes invasive gastroenteritis in humans, a disease involving significant penetration of the intestinal mucosa. However, few...