ProfessorPaulLangford

Sansone A, Watson PR, Wallis TS, Langford PR, Kroll JSet al., 2002, The role of two periplasmic copper- and zinc-cofactored superoxide dismutases in the virulence of <i>Salmonella choleraesuis</i>, MICROBIOLOGY-SGM, Vol: 148, Pages: 719-726, ISSN: 1350-0872

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• Citations: 44

Bossé JT, Janson H, Sheehan BJ, Beddek AJ, Rycroft AN, Kroll JS, Langford PRet al., 2002, <i>Actinobacillus pleuropneumoniae</i>:: pathobiology and pathogenesis of infection, MICROBES AND INFECTION, Vol: 4, Pages: 225-235, ISSN: 1286-4579

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• Citations: 283

Sansone A, Watson PR, Wallis TS, Langford PR, Kroll JSet al., 2002, The role of two periplasmic copper- and zinc-cofactored superoxide dismutases in the virulence of Salmonella choleraesuis, Microbiology, Vol: 148, Pages: 719-726, ISSN: 1350-0872

Periplasmic copper- and zinc-cofactored superoxide dismutases ([Cu,Zn]-SODs, SodC) of several Gram-negative pathogens can protect against superoxide-radical-mediated host defences, and thus contribute to virulence. This role has been previously defined for one [Cu,Zn]-SOD in various Salmonella serovars. Following the recent discovery of a second periplasmic [Cu,Zn]-SOD in Salmonella, the effect of knockout mutations in one or both of the original sodC-1 and the new sodC-2 on the virulence of the porcine pathogen Salmonella choleraesuis is investigated here. In comparison to wild-type, while sodC mutants - whether single or double - showed no impairment in growth, they all showed equally enhanced sensitivity to superoxide and a dramatically increased sensitivity to the combination of superoxide and nitric oxide in vitro. This observation had its correlate in experimental infection both ex vivo and in vivo. Mutation of sodC significantly impaired survival of S. choleraesuis in interferon γ-stimulated murine macrophages compared to wild-type organisms, and all S. choleraesuis sodC mutants persisted in significantly lower numbers than wild-type in BALB/c (Itys) and C3H/HeN (Ityr) mice after experimental infection, but in no experimental system were sodC-1 sodC-2 double mutants more attenuated than either single mutant. These data suggest that both [Cu,Zn]-SODs are needed to protect bacterial periplasmic or membrane components. While SodC plays a role in S. choleraesuis virulence, the data presented here suggest that this is through overcoming a threshold-effect, probably achieved by acquisition of sodC-1 on a bacteriophage. Loss of either sodC gene confers maximum vulnerability to superoxide on S. choleraesuis.

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• Citations: 43

Langford PR, Sheehan BJ, Shaikh T, Kroll JSet al., 2002, Active copper- and zinc-containing superoxide dismutase in the cryptic genospecies of <i>Haemophilus</i> causing urogenital and neonatal infections discriminates them from <i>Haemophilus influenzae</i> sensu stricto, JOURNAL OF CLINICAL MICROBIOLOGY, Vol: 40, Pages: 268-270, ISSN: 0095-1137

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• Citations: 13

Langford PR, Sansone A, Valenti P, Battistoni A, Kroll JSet al., 2002, Bacterial superoxide dismutase and virulence, SUPEROXIDE DISMUTASE, Vol: 349, Pages: 155-166, ISSN: 0076-6879

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• Citations: 12

Ali TR, Kroll JS, Langford PR, 2002, Haemophilus influenzae microarrays: virulence and vaccines, Comp Funct Genomics, Vol: 3, Pages: 358-361, ISSN: 1531-6912

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Pacello F, Langford PR, Kroll JS, Indiani C, Smulevich G, Desideri A, Rotilio G, Battistoni Aet al., 2001, A novel heme protein, the Cu,Zn-superoxide dismutase from <i>Haemophilus ducreyi</i>, JOURNAL OF BIOLOGICAL CHEMISTRY, Vol: 276, Pages: 30326-30334, ISSN: 0021-9258

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• Citations: 27

Battistoni A, Pacello F, Mazzetti AP, Capo C, Kroll JS, Langford PR, Sansone A, Donnarumma G, Valenti P, Rotilio Get al., 2001, A histidine-rich metal binding domain at the N terminus of Cu,Zn-superoxide dismutases from pathogenic bacteria, JOURNAL OF BIOLOGICAL CHEMISTRY, Vol: 276, Pages: 30315-30325, ISSN: 0021-9258

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• Citations: 54

Webb SAR, Langford PR, Kroll JS, 2001, A promoter probe plasmid based on green fluorescent protein: a strategy for studying meningococcal gene expression, Pages: 663-677, ISBN: 9780896038493

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Webb SAR, Langford PR, Kroll JS, 2001, A promoter probe plasmid based on green fluorescent protein, Methods in Molecular Medicine, Vol: 67, Pages: 663-677

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Pesce A, Battistoni A, Stroppolo ME, Polizio F, Nardini M, Kroll JS, Langford PR, O'Neill P, Sette M, Desideri A, Bolognesi Met al., 2000, Functional and crystallographic characterization of <i>Salmonella typhimurium</i> Cu,Zn superoxide dismutase coded by the <i>sodCI</i> virulence gene, JOURNAL OF MOLECULAR BIOLOGY, Vol: 302, Pages: 465-478, ISSN: 0022-2836

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• Citations: 43

Sheehan BJ, Langford PR, Rycroft AN, Kroll JSet al., 2000, [Cu,Zn]-superoxide dismutase mutants of the swine pathogen <i>Actinobacillus pleuropneumoniae</i> are unattenuated in infections of the natural host, INFECTION AND IMMUNITY, Vol: 68, Pages: 4778-4781, ISSN: 0019-9567

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• Citations: 30

Forest KT, Langford PR, Kroll JS, Getzoff EDet al., 2000, Cu,Zn superoxide dismutase structure from a microbial pathogen establishes a class with a conserved dimer interface, JOURNAL OF MOLECULAR BIOLOGY, Vol: 296, Pages: 145-153, ISSN: 0022-2836

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• Citations: 44

Pollard AJ, Galassini R, van der Voort EMR, Booy R, Langford P, Nadel S, Ison C, Kroll JS, Poolman J, Levin Met al., 1999, Humoral immune responses to <i>Neisseria meningitidis</i> in children, INFECTION AND IMMUNITY, Vol: 67, Pages: 2441-2451, ISSN: 0019-9567

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• Citations: 38

Pollard AJ, Galassini R, van der Voort EMR, Hibberd M, Booy R, Langford P, Nadel S, Ison C, Kroll JS, Poolman J, Levin Met al., 1999, Cellular immune responses to <i>Neisseria meningitidis</i> in children, INFECTION AND IMMUNITY, Vol: 67, Pages: 2452-2463, ISSN: 0019-9567

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• Citations: 27

, 1999, Neisserial vaccine compositions and methods, PCT/GB00/00624

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Kroll JS, Wilks KE, Farrant JL, Langford PRet al., 1998, Natural genetic exchange between <i>Haemophilus </i>and <i>Neisseria</i>:: Intergeneric transfer of chromosomal genes between major human pathogens, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, Vol: 95, Pages: 12381-12385, ISSN: 0027-8424

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• Citations: 118

, 1998, Superoxide dismutase as a vaccine antigen, PCT/GB99/02828

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Wilks KE, Dunn KLR, Farrant JL, Reddin KM, Gorringe AR, Langford PR, Kroll JSet al., 1998, Periplasmic superoxide dismutase in meningococcal pathogenicity, INFECTION AND IMMUNITY, Vol: 66, Pages: 213-217, ISSN: 0019-9567

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• Citations: 105

Cash P, Argo E, Langford PR, Kroll JSet al., 1997, Development of a Haemophilus two-dimensional protein database, ELECTROPHORESIS, Vol: 18, Pages: 1472-1482, ISSN: 0173-0835

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• Citations: 38

Farrant JL, Sansone A, Canvin JR, Pallen MJ, Langford PR, Wallis TS, Dougan G, Kroll JSet al., 1997, Bacterial copper- and zinc-cofactored superoxide dismutase contributes to the pathogenesis of systemic salmonellosis, MOLECULAR MICROBIOLOGY, Vol: 25, Pages: 785-796, ISSN: 0950-382X

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• Citations: 109

Farrant JL, Sansone A, Canvin JR, Pallen MJ, Langford PR, Wallis TS, Dougan G, Kroll JSet al., 1997, Bacterial copper- and zinc-cofactored superoxide dismutase contributes to the pathogenesis of systemic salmonellosis, Molecular Microbiology, Vol: 25, Pages: 785-796, ISSN: 0950-382X

Copper/zinc-cofactored superoxide dismutase ([Cu,Zn]-SOD) has been found in the periplasm of many bacterial species but its biological function is unknown. Here we report the cloning and characterization of sodC, encoding [Cu,Zn]-SOD, from Salmonella typhimurium. The predicted protein sequence shows only 58% identity to Escherichia coli SodC, and from this its chromosomal location and its immediate proximity to a phage gene, sodC, in Salmonella is speculated to have been acquired by bacteriophage-mediated horizontal transfer from an unknown donor. A sodC mutant of S. typhimurium was unimpaired on aerobic growth in rich medium but showed enhanced sensitivity in vitro to the microbicidal action of superoxide. S. typhimurium, S. choleraesuis and S. dublin sodC mutants showed reduced lethality in a mouse model of oral infection and persisted in significantly lower numbers in livers and spleens after intraperitoneal infection, suggesting that [Cu,Zn]-SOD plays a role in pathogenicity, protecting Salmonella against oxygen radical-mediated host defences. There was, however, no observable difference compared with wild type in the interaction of sodC mutants with porcine pleural, mouse peritoneal or J774 macrophages in vitro, perhaps reflecting the hierarchical capacity of different macrophage lines to kill Salmonella, the most efficient overwhelming the proposed protective effect of periplasmic SOD.

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DMello RA, Langford PR, Kroll JS, 1997, Role of bacterial Mn-cofactored superoxide dismutase in oxidative stress responses, nasopharyngeal colonization, and sustained bacteremia caused by Haemophilus influenzae type b, INFECTION AND IMMUNITY, Vol: 65, Pages: 2700-2706, ISSN: 0019-9567

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• Citations: 34

Langford PR, Kroll JS, 1997, Distribution, cloning, characterisation and mutagenesis of sodC, the gene encoding copper/zinc superoxide dismutase, a potential determinant of virulence, in Haemophilus ducreyi, FEMS IMMUNOLOGY AND MEDICAL MICROBIOLOGY, Vol: 17, Pages: 235-242, ISSN: 0928-8244

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• Citations: 9

Langford PR, Loynds BM, Kroll JS, 1996, Cloning and molecular characterization of Cu,Zn superoxide dismutase from Actinobacillus pleuropneumoniae, INFECTION AND IMMUNITY, Vol: 64, Pages: 5035-5041, ISSN: 0019-9567

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• Citations: 38

Lainson FA, Thomson N, Rowe HA, Langford PR, Aitchison KD, Donachie W, Kroll JSet al., 1996, Occurrence of [copper, zinc]-cofactored superoxide dismutase in Pasteurella haemolytica and its serotype distribution, FEMS MICROBIOLOGY LETTERS, Vol: 142, Pages: 11-17, ISSN: 0378-1097

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• Citations: 13

Canvin J, Langford PR, Wilks KE, Kroll JSet al., 1996, Identification of sodC encoding periplasmic [Cu,Zn]-superoxide dismutase in Salmonella, FEMS MICROBIOLOGY LETTERS, Vol: 136, Pages: 215-220, ISSN: 0378-1097

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• Citations: 41

KROLL JS, LANGFORD PR, WILKS KE, KEIL ADet al., 1995, BACTERIAL [CU,ZN]-SUPEROXIDE DISMUTASE - PHYLOGENETICALLY DISTINCT FROM THE EUKARYOTIC ENZYME, AND NOT SO RARE AFTER ALL, MICROBIOLOGY-UK, Vol: 141, Pages: 2271-2279, ISSN: 1350-0872

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• Citations: 115

Langford PR, 1994, Hib meningitis: here today, gone tomorrow?, Biologist, Vol: 41, Pages: 105-108

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KROLL JS, LANGFORD PR, SAAH JR, LOYNDS BMet al., 1993, MOLECULAR AND GENETIC-CHARACTERIZATION OF SUPEROXIDE-DISMUTASE IN HAEMOPHILUS-INFLUENZAE TYPE-B, MOLECULAR MICROBIOLOGY, Vol: 10, Pages: 839-848, ISSN: 0950-382X

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• Citations: 21