Imperial College London

DrBrianRobertson

Faculty of MedicineDepartment of Medicine

Reader in Systems Microbiology
 
 
 
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Contact

 

+44 (0)20 7594 3198b.robertson

 
 
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Assistant

 

Ms Sophie Kemp +44 (0)20 7594 3199

 
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Location

 

3.41Flowers buildingSouth Kensington Campus

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Summary

 

Publications

Publication Type
Year
to

96 results found

Young DB, Robertson BD, 2002, Immune intervention in tuberculosis, Immunology of Infectious Diseases, Pages: 439-451, ISBN: 9781555812140

BOOK CHAPTER

Ho TBL, Robertson BD, Rhee JT, Young DB, Small PM, Shaw RJet al., 2001, Are deletions in the PLCD locus associated with variation in infectivity in clinical isolates of Mycobacterium tuberculosis?, THORAX, Vol: 56, Pages: 56-56, ISSN: 0040-6376

JOURNAL ARTICLE

Young D, Robertson B, 2001, Genomics: leprosy - a degenerative disease of the genome., Current Biology, Vol: 11

JOURNAL ARTICLE

Young D, Robertson B, 2001, Genomics: leprosy - a degenerative disease of the genome., Curr Biol, Vol: 11, Pages: R381-R383, ISSN: 0960-9822

Analysis of the genome of the leprosy bacillus uncovers evidence of extensive deletion and inactivation of genes. Secluded in a specialised niche, it has discarded much of its genetic heritage, though retaining just enough to be a major human pathogen.

JOURNAL ARTICLE

De Smet KAL, Weston A, Brown IN, Young DB, Robertson BDet al., 2000, Three pathways for trehalose biosynthesis in mycobacteria, MICROBIOLOGY-UK, Vol: 146, Pages: 199-208, ISSN: 1350-0872

JOURNAL ARTICLE

Devyatyrova-Johnson M, Rees IH, Robertson BD, Turner MW, Klein NJ, Jack DLet al., 2000, The lipopolysaccharide structures of Salmonella enterica serovar Typhimurium and Neisseria gonorrhoeae determine the attachment of human mannose-binding lectin to intact organisms, INFECTION AND IMMUNITY, Vol: 68, Pages: 3894-3899, ISSN: 0019-9567

JOURNAL ARTICLE

Dockrell HM, Brahmbhatt S, Robertson BD, Britton S, Fruth U, Gebre N, Hunegnaw M, Hussain R, Manadhar R, Murrillo L, Pessolani MCV, Roche P, Salgado JL, Sampaio E, Shahid F, Thole JER, Young DBet al., 2000, Diagnostic assays for leprosy based on T-cell epitopes, Workshop on Leprosy Research at the New Millennium, Publisher: LEPRA, Pages: S55-S58, ISSN: 0305-7518

CONFERENCE PAPER

Dockrell HM, Brahmbhatt S, Robertson BD, Britton S, Fruth U, Gebre N, Hunegnaw M, Hussain R, Manandhar R, Murillo L, Pessolani MCV, Roche P, Salgado JL, Sampaio E, Shahid F, Thole JER, Young DBet al., 2000, A postgenomic approach to identification of Mycobacterium leprae-specific peptides as T-cell reagents, INFECTION AND IMMUNITY, Vol: 68, Pages: 5846-5855, ISSN: 0019-9567

JOURNAL ARTICLE

Herrmann JL, Delahay R, Gallagher A, Robertson B, Young Det al., 2000, Analysis of post-translational modification of mycobacterial proteins using a cassette expression system., FEBS Lett, Vol: 473, Pages: 358-362, ISSN: 0014-5793

A recombinant expression system was developed to analyse sequence determinants involved in O-glycosylation of proteins in mycobacteria. By expressing peptide sequences corresponding to known glycosylation sites within a chimeric lipoprotein construct, amino acids flanking modified threonine residues were found to have an important influence on glycosylation. The expression system was used to screen mycobacterial sequences selected using a neural network (NetOglyc) trained on eukaryotic O-glycoproteins. Evidence of glycosylation was obtained for eight of 11 proteins tested. The results suggest that sites involved in O-glycosylation of mycobacterial and eukaryotic proteins share similar structural features.

JOURNAL ARTICLE

Ho TBL, Robertson BD, Taylor GM, Shaw RJ, Young DBet al., 2000, Comparison of Mycobacterium tuberculosis genomes reveals frequent deletions in a 20 kb variable region in clinical isolates, YEAST, Vol: 17, Pages: 272-282, ISSN: 0749-503X

JOURNAL ARTICLE

Young DB, Robertson BD, 1999, TB vaccines: global solutions for global problems., Science, Vol: 284, Pages: 1479-1480, ISSN: 0036-8075

JOURNAL ARTICLE

Young DB, Robertson BD, 1999, Microbiology - TB vaccines: Global solutions for global problems, SCIENCE, Vol: 284, Pages: 1479-1480, ISSN: 0036-8075

JOURNAL ARTICLE

Gill MJ, Simjee S, Al-Hattawi K, Robertson BD, Easmon CSF, Ison CAet al., 1998, Gonococcal resistance to beta-lactams and tetracycline involves mutation in loop 3 of the porin encoded at the penB locus, ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, Vol: 42, Pages: 2799-2803, ISSN: 0066-4804

JOURNAL ARTICLE

Young DB, Robertson BD, 1998, Commentary - Approaches to combat tuberculosis, CURRENT OPINION IN BIOTECHNOLOGY, Vol: 9, Pages: 650-652, ISSN: 0958-1669

JOURNAL ARTICLE

Delahay RM, Robertson BD, Balthazar JT, Shafer WM, Ison CAet al., 1997, Involvement of the gonococcal MtrE protein in the resistance of Neisseria gonorrhoeae to toxic hydrophobic agents, MICROBIOLOGY-UK, Vol: 143, Pages: 2127-2133, ISSN: 1350-0872

JOURNAL ARTICLE

Goyal M, Shaw RJ, Banerjee DK, Coker RJ, Robertson BD, Young DBet al., 1997, Rapid detection of multidrug-resistant tuberculosis, EUROPEAN RESPIRATORY JOURNAL, Vol: 10, Pages: 1120-1124, ISSN: 0903-1936

JOURNAL ARTICLE

Heyderman RS, Klein NJ, Daramola OA, Hammerschmidt S, Frosch M, Robertson BD, Levin M, Ison CAet al., 1997, Induction of human endothelial tissue factor expression by Neisseria meningitidis: The influence of bacterial killing and adherence to the endothelium, MICROBIAL PATHOGENESIS, Vol: 22, Pages: 265-274, ISSN: 0882-4010

JOURNAL ARTICLE

Petering H, Hammerschmidt S, Frosch M, vanPutten JPM, Ison CA, Robertson BDet al., 1996, Genes associated with the meningococcal capsule complex are also found in Neisseria gonorrhoeae, JOURNAL OF BACTERIOLOGY, Vol: 178, Pages: 3342-3345, ISSN: 0021-9193

JOURNAL ARTICLE

GEMS D, FERGUSON CJ, ROBERTSON BD, NIEVES R, PAGE AP, BLAXTER ML, MAIZELS RMet al., 1995, AN ABUNDANT, TRANS-SPLICED MESSENGER-RNA FROM TOXOCARA-CANIS INFECTIVE LARVAE ENCODES A 26-KDA PROTEIN WITH HOMOLOGY TO PHOSPHATIDYLETHANOLAMINE-BINDING PROTEINS, JOURNAL OF BIOLOGICAL CHEMISTRY, Vol: 270, Pages: 18517-18522, ISSN: 0021-9258

JOURNAL ARTICLE

Schwan ET, Robertson BD, Brade H, van Putten JPet al., 1995, Gonococcal rfaF mutants express Rd2 chemotype LPS and do not enter epithelial host cells., Mol Microbiol, Vol: 15, Pages: 267-275, ISSN: 0950-382X

We have investigated the function of the Isi-1 gene of Neisseria gonorrhoeae previously implicated in lipopolysaccharide (LPS)-inner-core biosynthesis (Petricoin et al., 1991). Disruption of the gene in gonococcal strain MS11 resulted in the production of LPS that migrated faster than that from an isogenic galE mutant, typical for a mutation that influences the inner-core region. Complementation of a panel of Salmonella typhimurium mutants with defined defects in rfa loci demonstrated conclusively that the Isi-1 gene of MS11 is functionally homologous to the rfaF gene, which encodes heptosyltransferase II in both E. coli and S. typhimurium. Comparison of deduced amino acid sequences of the gonococcal and the Salmonella RfaF demonstrated 70% similarity, including 47% identical amino acid residues. Immunochemical analysis of the LPS using monoclonal antibodies directed against chemically defined inner-core glycoconjugates revealed that the gonococcal and Salmonella Rd2-chemotypes were antigenically similar, further extending the genetic and functional homology. Infection experiments in vitro demonstrated that the Isi-1 mutant could not invade human Chang epithelial cells despite expression of a genetically defined invasion-promoting gonococcal opacity protein. These data imply that the LPS phenotype is a critical factor for gonococcal invasiveness.

JOURNAL ARTICLE

van Putten JP, Grassmé HU, Robertson BD, Schwan ETet al., 1995, Function of lipopolysaccharide in the invasion of Neisseria gonorrhoeae into human mucosal cells., Prog Clin Biol Res, Vol: 392, Pages: 49-58, ISSN: 0361-7742

The variable incorporation of sialic acid into the LPS of Neisseria gonorrhoeae modulates the invasive behavior of this bacterium towards cultured human epithelial cells. Here we report that the inhibitory effect of LPS sialylation on the gonococcal entry into Chang epithelial cells and ME-180 endocervical cells (van Putten, EMBO J 12:4043-4051, 1993) is located early in the uptake pathway upstream of the invasion-associated recruitment of F-actin at the sites of bacterial entry, but beyond the level of bacterial adherence. Receptor equilibrium studies using purified radiolabelled opacity protein receptor demonstrated that LPS sialylation caused a 3-5 fold reduction in binding of the bacterial invasion-promoting opacity outer membrane protein to its receptor. In HEC-1B and PC-3 cells, LPS sialylation did only partially inhibit the bacterial entry process, suggesting the existence of a second uptake mechanism for gonococci in these cell lines. Experiments with non-sialylatable and truncated isogenic LPS variants, and with genetically defined LPS mutants demonstrated that the invasive phenotype of N. gonorrhoeae requires a minimum of an Rc (or Rd1) chemotype of LPS. Variation within the LPS outer core region did not influence the invasive properties of the bacteria as long as there was no attached sialic acid.

JOURNAL ARTICLE

van Putten JP, Robertson BD, 1995, Molecular mechanisms and implications for infection of lipopolysaccharide variation in Neisseria., Mol Microbiol, Vol: 16, Pages: 847-853, ISSN: 0950-382X

The lipopolysaccharides of the pathogenic Neisseria species are subject to structural variation owing to a combination of intrinsic changes in lipopolysaccharide (LPS) biosynthesis and external modification of the LPS molecule with sialic acid. This variation appears to control bacterial behaviour by altering their ability to interact with human cells and to evade host immune defences. This interconversion of LPS phenotypes, which is also observed during the natural infection, is probably due to environmental regulation of LPS biosynthesis superimposed on spontaneous changes in the DNA of distinct LPS loci. LPS variation may be a common strategy of mucosal pathogens to colonize and persist within the human host.

JOURNAL ARTICLE

Hammerschmidt S, Birkholz C, Zähringer U, Robertson BD, van Putten J, Ebeling O, Frosch Met al., 1994, Contribution of genes from the capsule gene complex (cps) to lipooligosaccharide biosynthesis and serum resistance in Neisseria meningitidis., Mol Microbiol, Vol: 11, Pages: 885-896, ISSN: 0950-382X

Within the capsule gene complex (cps) of Neisseria meningitidis B a 5.5 kb DNA fragment encodes proteins with strong homologies to enzymes of the lipopolysaccharide biosynthetic pathway of Salmonella typhimurium and Escherichia coli, GalE, RfbB, RfbC and RfbD. A meningococcal galE mutant expressed a truncated lipooligosaccharide (LOS), which terminated at the glucose residue between inner and outer core, and a second galE gene present outside the cps cluster was found to be transcriptionally and functionally inactive and, thus, unable to complement this defect. Because of the defect in the outer core, the LOS of the galE-defective meningococcal mutant was not sialylated. In contrast, carbohydrate analysis of the LOS of an rfb-defective meningococcal mutant revealed no difference from the LOS of the wild-type strain, suggesting that the rfb genes are inactive. This was supported by Northern blot analysis, which showed that expression of the rfb gene products was transcriptionally regulated. The inability of the meningococcal galE mutant, which cannot sialylate the LOS, allowed us to investigate the significance of LOS sialylation in relation to the presence of the polysialic acid capsule. Sialylated LOS, but not the polysialic acid capsule, is necessary to confer complete serum resistance on the meningococcus by inhibition of the alternative complement pathway.

JOURNAL ARTICLE

Robertson BD, Frosch M, van Putten JP, 1994, The identification of cryptic rhamnose biosynthesis genes in Neisseria gonorrhoeae and their relationship to lipopolysaccharide biosynthesis., J Bacteriol, Vol: 176, Pages: 6915-6920, ISSN: 0021-9193

Neisseria gonorrhoeae synthesizes a rough lipopolysaccharide that does not contain any of the repetitive units characteristic of the smooth lipopolysaccharide of members of the family Enterobacteriaceae. Three gonococcal homologs of Salmonella serovar typhimurium genes involved in the synthesis of the rhamnose component of the repetitive subunits have been isolated. Gonococcal homologs for rfbB, rfbA, and rfbD were found downstream of the galE gene in a region of the chromosome which shows overall homology with the meningococcal capsule gene complex region D. Sequence alignment demonstrated that the gonococcal gene products have 69, 65, and 54% amino acid identity with the Salmonella proteins RfbB, RfbA, and RfbD. The gonococcal RfbB and RfbA amino acid sequences share even more identical residues (73 and 65%, respectively) with the amino acid sequences derived from Escherichia coli genes o355 and o292, respectively. These genes are clustered with the genes involved in the biosynthesis of enterobacterial common antigen, and o355 is listed in the GenBank and Swiss Protein data banks as rffE (encoding UDP-GlcNAc-2-epimerase). However, complementation studies demonstrated that o355 does not encode the enzyme UDP-GlcNAc-2-epimerase. Gonococcal strains constructed with null mutations in the rfbBAD genes were unchanged in lipopolysaccharide phenotype and in the synthesis of gonococcal carbohydrate-containing C antigen. We were unable to detect any changes in gonococcal phenotype with respect to lipopolysaccharide sialylation, monoclonal-antibody binding, serum sensitivity, or interaction with eukaryotic cells in vitro. We conclude that the absence of a homolog for rfbC precludes the existence of a functional dTDP-rhamnose biosynthesis pathway in the gonococcal strains examined and that these genes are only maintained in N. gonorrhoeae either because of the presence of the galE gene or because of another as yet unrecognized function.

JOURNAL ARTICLE

GILLESPIE SH, BIDWELL D, VOLLER A, ROBERTSON BD, MAIZELS RMet al., 1993, DIAGNOSIS OF HUMAN TOXOCARIASIS BY ANTIGEN CAPTURE ENZYME-LINKED-IMMUNOSORBENT-ASSAY, JOURNAL OF CLINICAL PATHOLOGY, Vol: 46, Pages: 551-554, ISSN: 0021-9746

JOURNAL ARTICLE

Robertson BD, Frosch M, van Putten JP, 1993, The role of galE in the biosynthesis and function of gonococcal lipopolysaccharide., Mol Microbiol, Vol: 8, Pages: 891-901, ISSN: 0950-382X

Lipopolysaccharide is an essential component of the outer membrane of Gram-negative bacteria and an important virulence factor of many pathogens, such as Neisseria gonorrhoeae. We have cloned the gonococcal galE gene which was found to be located in the gonococcal homologue of the meningococcal capsule gene complex region D. Sequence alignment indicated extensive homology with the Escherichia coli and Salmonella GalE proteins. Mutants with insertions in the galE gene were used as a tool to characterize the structure and function of gonococcal lipopolysaccharide. They displayed deep rough phenotypes, and chemical analysis confirmed the loss of galactose from the mutant lipopolysaccharide. Functional analysis indicated that the terminal oligosaccharides contain galactose and that these are lost in galE mutants. The importance of these oligosaccharides in gonococcal biology is clear from the fact that they contain the epitopes that are the targets for killing by normal human serum, and the acceptor site for sialic acid, which acts to protect the gonococcus from this killing. Furthermore, infection experiments in vitro indicate that the galE mutants exhibit unaltered intergonococcal adhesion as well as adhesion to, and invasion of, epithelial cells.

JOURNAL ARTICLE

Robertson BD, Meyer TF, 1992, Genetic variation in pathogenic bacteria., Trends Genet, Vol: 8, Pages: 422-427, ISSN: 0168-9525

In contrast to textbook ideas of pure cultures and defined strains, genetic variation is a fact of life in the microbial world. It not only allows pathogens to establish themselves in their chosen host, but also allows them to resist that host's subsequent attempts to evict them. Here we review some of the mechanisms that bring about this variation, and some of the functional consequences that result from it.

JOURNAL ARTICLE

BIANCO AE, ROBERTSON BD, KUO YM, TOWNSON S, HAM PJet al., 1990, DEVELOPMENTALLY REGULATED EXPRESSION AND SECRETION OF A POLYMORPHIC ANTIGEN BY ONCHOCERCA INFECTIVE-STAGE LARVAE, MOLECULAR AND BIOCHEMICAL PARASITOLOGY, Vol: 39, Pages: 203-212, ISSN: 0166-6851

JOURNAL ARTICLE

ROBERTSON BD, BIANCO AT, MCKERROW JH, MAIZELS RMet al., 1989, TOXOCARA-CANIS - PROTEOLYTIC-ENZYMES SECRETED BY THE INFECTIVE LARVAE INVITRO, EXPERIMENTAL PARASITOLOGY, Vol: 69, Pages: 30-36, ISSN: 0014-4894

JOURNAL ARTICLE

ROBERTSON BD, BURKOT TR, GILLESPIE SH, KENNEDY MW, WAMBAI Z, MAIZELS RMet al., 1988, DETECTION OF CIRCULATING PARASITE ANTIGEN AND SPECIFIC ANTIBODY IN TOXOCARA-CANIS INFECTIONS, CLINICAL AND EXPERIMENTAL IMMUNOLOGY, Vol: 74, Pages: 236-241, ISSN: 0009-9104

JOURNAL ARTICLE

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