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

107 results found

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.

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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.

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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

ROBERTSON BD, KWANLIM GE, MAIZELS RM, 1988, A SENSITIVE MICROPLATE ASSAY FOR THE DETECTION OF PROTEOLYTIC-ENZYMES USING RADIOLABELED GELATIN, ANALYTICAL BIOCHEMISTRY, Vol: 172, Pages: 284-287, ISSN: 0003-2697

JOURNAL ARTICLE

BUNDY DAP, THOMPSON DE, ROBERTSON BD, COOPER ESet al., 1987, AGE-RELATIONSHIPS OF TOXOCARA CANIS SEROPOSITIVITY AND GEOHELMINTH INFECTION PREVALENCE IN 2 COMMUNITIES IN ST-LUCIA, WEST-INDIES, TROPICAL MEDICINE AND PARASITOLOGY, Vol: 38, Pages: 309-312, ISSN: 0177-2392

JOURNAL ARTICLE

MAIZELS RM, KENNEDY MW, MEGHJI M, ROBERTSON BD, SMITH HVet al., 1987, SHARED CARBOHYDRATE EPITOPES ON DISTINCT SURFACE AND SECRETED ANTIGENS OF THE PARASITIC NEMATODE TOXOCARA-CANIS, JOURNAL OF IMMUNOLOGY, Vol: 139, Pages: 207-214, ISSN: 0022-1767

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RATHAUR S, ROBERTSON BD, SELKIRK ME, MAIZELS RMet al., 1987, SECRETORY ACETYLCHOLINESTERASES FROM BRUGIA-MALAYI ADULT AND MICROFILARIAL PARASITES, MOLECULAR AND BIOCHEMICAL PARASITOLOGY, Vol: 26, Pages: 257-265, ISSN: 0166-6851

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ROBERTSON BD, RATHAUR S, MCKERROW JH, MAIZELS RMet al., 1987, FUNCTIONAL ANALYSES OF THE EXCRETORY-SECRETORY MOLECULES OF TOXOCARA-CANIS INFECTIVE LARVAE, JOURNAL OF CELLULAR BIOCHEMISTRY, Pages: 172-172, ISSN: 0730-2312

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Robertson BD, Rathaur S, Maizels RM, 1987, Antigenic and biochemical analyses of the excretory-secretory molecules of Toxocara canis infective larvae., Current topics in veterinary medicine and animal science., Vol: 43, Pages: 167-173, ISSN: 0166-2333

JOURNAL ARTICLE

Li Y, Spiropoulos J, Cooley J, Khara J, Gladstone C, Asai M, Bosse J, Robertson B, Newton SM, Langford Pet al., Galleria mellonella - a novel infection model for the Mycobacterium tuberculosis complex, Virulence, ISSN: 2150-5594

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