<b>Use of the complete genome sequence information of <i>Haemophilus influenzae</i> strain Rd to investigate lipopolysaccharide biosynthesis</b>

Hood, Derek W.; Deadman, Mary E.; Allen, T.; Masoud, Hussein; Martin, Andrew; Brisson, Jean Robert; Fleischmann, Robert; Venter, J. Craig; Richards, James C.; Moxon, E. Richard

doi:10.1046/j.1365-2958.1996.01545.x

Cited by 155 publications

(207 citation statements)

References 40 publications

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“…Strains with a deficiency in UDP-glucose production exhibit a number of phenotypes, including an altered LPS profile (21,32) and increased susceptibility to hydrophobic agents, bile salts, and cationic antimicrobial peptides (32). Similarly, the V. fischeri pgm mutant displayed a decrease in phosphoglucomutase activity, grew poorly on MM-galactose, exhibited an altered LPS profile, and displayed an increased susceptibility to polymyxin B, deoxycholate, and SDS.…”

Section: Discussionmentioning

confidence: 99%

“…These interactions give strength and rigidity to the otherwise fluid outer membrane. H. influenzae pgm mutants, presumably defective for UDP-glucose synthesis, contain LPS species with a reduced number of sugar residues in the inner core (21). If the pgm mutation caused a parallel defect on the inner core of V. fischeri LPS, which would not be surprising given the conserved nature of LPS structure among gramnegative bacteria (16), then the strength of the outer membrane likely would be reduced.…”

Section: Discussionmentioning

confidence: 99%

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Role for Phosphoglucomutase in Vibrio fischeri-Euprymna scolopes Symbiosis

2002

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Vibrio fischeri, a luminescent marine bacterium, specifically colonizes the light organ of its symbiotic partner, the Hawaiian squid Euprymna scolopes. In a screen for V. fischeri colonization mutants, we identified a strain that exhibited on average a 10-fold decrease in colonization levels relative to that achieved by wild-type V. fischeri. Further characterization revealed that this defect did not result from reduced luminescence or motility, two processes required for normal colonization. We determined that the transposon in this mutant disrupted a gene with high sequence identity to the pgm (phosphoglucomutase) gene of Escherichia coli, which encodes an enzyme that functions in both galactose metabolism and the synthesis of UDP-glucose. The V. fischeri mutant grew poorly with galactose as a sole carbon source and was defective for phosphoglucomutase activity, suggesting functional identity between E. coli Pgm and the product of the V. fischeri gene, which was therefore designated pgm. In addition, lipopolysaccharide profiles of the mutant were distinct from that of the parent strain and the mutant exhibited increased sensitivity to various cationic agents and detergents. Chromosomal complementation with the wild-type pgm allele restored the colonization ability to the mutant and also complemented the other noted defects. Unlike the pgm mutant, a galactose-utilization mutant (galK) of V. fischeri colonized juvenile squid to wild-type levels, indicating that the symbiotic defect of the pgm mutant is not due to an inability to catabolize galactose. Thus, pgm represents a new gene required for promoting colonization of E. scolopes by V. fischeri.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Role for Phosphoglucomutase in Vibrio fischeri-Euprymna scolopes Symbiosis

2002

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“…Similarly, an essential function of pathogens is evasion of the host response defense mechanisms: pathogens such as Haemophilus influenzae, Helicobacter pylori, Escherichia coli, and Plasmodium falciparum (99,465) all show extreme variation in the targets of the immune system. The presence of simple repeats in prokaryotic DNA sequences has been associated (217,218) with the concept of contingency genes linked to phase variation of gene expression in pathogens (328). Strategies which combine search algorithms for detecting such repeats with the ability to display genome annotation, and specifically locating them relative to ORFs of known function, can identify targets that are critical to virulence (403).…”

Section: Genomicsmentioning

confidence: 99%

Search and Discovery Strategies for Biotechnology: the Paradigm Shift

Bull

Ward

Goodfellow

2000

Microbiol Mol Biol Rev

418

250

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SUMMARY Profound changes are occurring in the strategies that biotechnology-based industries are deploying in the search for exploitable biology and to discover new products and develop new or improved processes. The advances that have been made in the past decade in areas such as combinatorial chemistry, combinatorial biosynthesis, metabolic pathway engineering, gene shuffling, and directed evolution of proteins have caused some companies to consider withdrawing from natural product screening. In this review we examine the paradigm shift from traditional biology to bioinformatics that is revolutionizing exploitable biology. We conclude that the reinvigorated means of detecting novel organisms, novel chemical structures, and novel biocatalytic activities will ensure that natural products will continue to be a primary resource for biotechnology. The paradigm shift has been driven by a convergence of complementary technologies, exemplified by DNA sequencing and amplification, genome sequencing and annotation, proteome analysis, and phenotypic inventorying, resulting in the establishment of huge databases that can be mined in order to generate useful knowledge such as the identity and characterization of organisms and the identity of biotechnology targets. Concurrently there have been major advances in understanding the extent of microbial diversity, how uncultured organisms might be grown, and how expression of the metabolic potential of microorganisms can be maximized. The integration of information from complementary databases presents a significant challenge. Such integration should facilitate answers to complex questions involving sequence, biochemical, physiological, taxonomic, and ecological information of the sort posed in exploitable biology. The paradigm shift which we discuss is not absolute in the sense that it will replace established microbiology; rather, it reinforces our view that innovative microbiology is essential for releasing the potential of microbial diversity for biotechnology penetration throughout industry. Various of these issues are considered with reference to deep-sea microbiology and biotechnology.

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“…This HepIV residue can be substituted by further hexose extensions (Houliston et al, 2007;Månsson et al, 2003b), can be branched (Månsson et al, 2003a) or can be substituted by phosphocholine (PCho) (Fox et al, 2008). The gene repertoire required for the synthesis of the H. influenzae LPS molecule has been identified in a number of key strains (Hood et al, 1996a(Hood et al, , 2001 following analyses based upon the whole-genome sequence of strain Rd (Fleischmann et al, 1995). However, the genes responsible for the incorporation of HepIV and its substitution were not identified by these methods, as these LPS epitopes, and presumably their genetic determinants, are not found in strain Rd.…”

Section: Introductionmentioning

confidence: 99%

“…The patterns of LPS isolated from strains upon Tricine-SDS-PAGE (T-SDS-PAGE) were analysed as described previously (Hood et al, 1996a).…”

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confidence: 99%

Genes required for the synthesis of heptose-containing oligosaccharide outer core extensions in Haemophilus influenzae lipopolysaccharide

et al. 2010

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Heptose-containing oligosaccharides (OSs) are found in the outer core of the lipopolysaccharide (LPS) of a subset of non-typable Haemophilus influenzae (NTHi) strains. Candidate genes for the addition of either L-glycero-D-manno-heptose (LD-Hep) or D-glycero-D-manno-heptose (DD-Hep) and subsequent hexose sugars to these OSs have been identified from the recently completed genome sequences available for NTHi strains. losA1/losB1 and losA2/losB2 are two sets of related genes in which losA has homology to genes encoding glycosyltransferases and losB to genes encoding heptosyltransferases. Each set of genes is variably present across NTHi strains and is located in a region of the genome with an alternative gene organization between strains that contributes to LPS heterogeneity. Dependent upon the strain background, the LPS phenotype, structure and serum resistance of strains mutated in these genes were altered when compared with the relevant parent strain. Our studies confirm that losB1 and losB2 usually encode DDheptosyl-and LD-heptosyl transferases, respectively, and that losA1 and losA2 encode glycosyltransferases that play a role in OS extensions of NTHi LPS.

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**Use of the complete genome sequence information of Haemophilus influenzae strain Rd to investigate lipopolysaccharide biosynthesis**

Cited by 155 publications

References 40 publications

Role for Phosphoglucomutase in Vibrio fischeri-Euprymna scolopes Symbiosis

Role for Phosphoglucomutase in Vibrio fischeri-Euprymna scolopes Symbiosis

Search and Discovery Strategies for Biotechnology: the Paradigm Shift

Genes required for the synthesis of heptose-containing oligosaccharide outer core extensions in Haemophilus influenzae lipopolysaccharide

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