Haemophilus b Conjugate Vaccines

Vella, Philip P.; Ellis, Ronald W.

doi:10.1016/b978-0-7506-9265-6.50007-5

Cited by 7 publications

(6 citation statements)

References 76 publications

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“…Before the introduction of the Hib vaccination (Vella and Ellis, 1992) between 1985 and 1991, Hib‐related infections were the leading cause of childhood bacterial meningitis (Truk, 1984; Funkhouser et al ., 1991). The burden of disease caused by non‐type b H. influenzae currently necessitates treatment rather than prevention.…”

Section: Discussionmentioning

confidence: 99%

NADP and NAD utilization in Haemophilus influenzae

Reidl

Schlör

Kraiss

et al. 2000

Molecular Microbiology

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SummaryExogenous NAD utilization or pyridine nucleotide cycle metabolism is used by many bacteria to maintain NAD turnover and to limit energy-dependent de novo NAD synthesis. The genus Haemophilus includes several important pathogenic bacterial species that require NAD as an essential growth factor. The molecular mechanisms of NAD uptake and processing are understood only in part for Haemophilus. In this report, we present data showing that the outer membrane lipoprotein e(P4), encoded by the hel gene, and an exported 5 H -nucleotidase (HI0206), assigned as nadN, are necessary for NAD and NADP utilization. Lipoprotein e(P4) is characterized as an acid phosphatase that uses NADP as substrate. Its phosphatase activity is inhibited by compounds such as adenosine or NMN. The nadN gene product was characterized as an NAD-nucleotidase, responsible for the hydrolysis of NAD. H. influenzae hel and nadN mutants had defined growth deficiencies. For growth, the uptake and processing of the essential cofactors NADP and NAD required e(P4) and 5 H -nucleotidase. In addition, adenosine was identified as a potent growth inhibitor of wild-type H. influenzae strains, when NADP was used as the sole source of nicotinamide-ribosyl.

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Section: Discussionmentioning

confidence: 99%

NADP and NAD utilization in Haemophilus influenzae

Reidl

Schlör

Kraiss

et al. 2000

Molecular Microbiology

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“…Haemophilus influenzae is a facultative anaerobic organism which only exists in close association with its human host, and causes significant morbidity and mortality (Erwin and Smith, 2007;Vella and Ellis, 1992). Computational as well as experimental analyses revealed that, compared to E. coli, the genome of H. influenzae apparently harbours a reduced number of antioxidative systems Vergauwen et al, 2003;Pauwels et al, 2004;Harrison et al, 2007).…”

Section: Introductionmentioning

confidence: 98%

Transposon insertion in a serine-specific minor tRNA coding sequence affects intraperitoneal survival of Haemophilus influenzae in the infant rat model

Gerlach

Anthony

Deadman

et al. 2010

International Journal of Medical Microbiology

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“…Prior to the successful introduction of the H. influenzae type b conjugate vaccine, H. influenzae type b infections were the main cause of bacterial meningitis (42). H. influenzae is still a major cause of otitis media and pneumonia.…”

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confidence: 99%

PnuC and the Utilization of the Nicotinamide Riboside Analog 3-Aminopyridine inHaemophilus influenzae

Sauer

Merdanovic

Mortimer

et al. 2004

Antimicrob Agents Chemother

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The utilization pathway for the uptake of NAD and nicotinamide riboside was previously characterized for Haemophilus influenzae. We now report on the cellular location, topology, and substrate specificity of PnuC. pnuC of H. influenzae is only distantly related to pnuC of Escherichia coli and Salmonella enterica serovar Typhimurium. When E. coli PnuC was expressed in an H. influenzae pnuC mutant, it was able to take up only nicotinamide riboside and not nicotinamide mononucleotide. Therefore, we postulated that PnuC transporters in general possess specificity for nicotinamide riboside. Earlier studies showed that 3-aminopyridine derivatives (e.g., 3-aminopyridine adenine dinucleotide) are inhibitory for H. influenzae growth. By testing characterized strains with mutations in the NAD utilization pathway, we show that 3-aminopyridine riboside is inhibitory to H. influenzae and is taken up by the NAD-processing and nicotinamide riboside route. 3-Aminopyridine riboside is utilized effectively in a pnuC ؉ background. In addition, we demonstrate that 3-aminopyridine adenine dinucleotide resynthesis is produced by NadR. 3-Aminopyridine riboside-resistant H. influenzae isolates were characterized, and mutations in nadR could be detected. We also tested other species of the family Pasteurellaceae, Pasteurella multocida and Actinobacillus actinomycetemcomitans, and found that 3-aminopyridine riboside does not act as a growth inhibitor; hence, 3-aminopyridine riboside represents an anti-infective agent with a very narrow host range.

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Haemophilus b Conjugate Vaccines

Cited by 7 publications

References 76 publications

NADP and NAD utilization in Haemophilus influenzae

NADP and NAD utilization in Haemophilus influenzae

Transposon insertion in a serine-specific minor tRNA coding sequence affects intraperitoneal survival of Haemophilus influenzae in the infant rat model

PnuC and the Utilization of the Nicotinamide Riboside Analog 3-Aminopyridine inHaemophilus influenzae

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