The heme-binding lipoprotein (HbpA) of<i>Haemophilus influenzae</i>: Role in heme utilization

Morton, Daniel J.; Madore, Larissa L.; Smith, Ann; VanWagoner, Timothy M.; Seale, Thomas W.; Whitby, Paul W.; Stull, Terrence L.

doi:10.1016/j.femsle.2005.09.016

Cited by 47 publications

(68 citation statements)

References 32 publications

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“…Human serum albumin (HSA), and haemin were purchased from Sigma. Stock haem solutions were prepared at 1 mg haem ml 21 as previously described (Morton et al, 2005). Haemoglobin was dissolved in water immediately before use.…”

Section: Methodsmentioning

confidence: 99%

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The haem–haemopexin utilization gene cluster (hxuCBA) as a virulence factor of Haemophilus influenzae

et al. 2007

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Haemophilus influenzae has an absolute growth requirement for a porphyrin source, which can be supplied in vitro by haem, haemoglobin, or the haemoglobin-haptoglobin, haem-haemopexin and haem-albumin complexes. Utilization of the haem-haemopexin complex is known to be mediated by the products of the hxuCBA gene cluster. It was demonstrated that hxuC, but not hxuA or hxuB, is also essential for the utilization of haem from haem-albumin complexes. Mutants of the type b strain E1a lacking genes in the hxuCBA gene cluster were examined for their ability to cause bacteraemia in rat models of invasive disease. In 5-day-old rats, mutants in the hxuCBA genes yielded a significantly reduced bacteraemic titre compared to the wild-type strain. In addition, 5-day-old rats infected with the hxuCBA mutant strains exhibited significantly improved survival rates compared to those infected with the wild-type strain. Mutations in the haemoglobin/haemoglobinhaptoglobin-binding protein genes (hgps), either alone or in combination with the hxuCBA mutations, had no impact on virulence in 5-day-old rats. In 30-day-old rats infected with either the hxuCBA mutants or the wild-type strains, there was no significant difference in the ability to establish bacteraemia although bacterial titres were lower in rats infected with the hxuCBA mutants than in those infected with the wild-type strain. These age-related differences in the impact of mutations in the hxuCBA gene cluster may be related to changes in levels of host haem-binding proteins during development of the rat.

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Section: Methodsmentioning

confidence: 99%

“…Growth studies were performed in hdBHI supplemented as appropriate, using the Bioscreen C Microbiology Reader (Oy Growth Curves AB Ltd) as previously described (Morton et al, 2005(Morton et al, , 2006a.…”

Section: Methodsmentioning

confidence: 99%

The haem–haemopexin utilization gene cluster (hxuCBA) as a virulence factor of Haemophilus influenzae

et al. 2007

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“…Growth studies were performed using the Bioscreen C Microbiology Reader (Oy Growth Curves AB Ltd., Helsinki, Finland) as previously described [13].…”

Section: Growth Studiesmentioning

confidence: 99%

Lipoprotein e (P4) of Haemophilus influenzae: role in heme utilization and pathogenesis

Morton

Smith

VanWagoner

et al. 2007

Microbes and Infection

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Lipoprotein e (P4) of Haemophilus influenzae is a phosphomonoesterase, encoded by the hel gene, that has been implicated in the acquisition of heme by this fastidious organism. However, lipoprotein e (P4) is also involved in the utilization of NAD and NMN. Some reports have concluded that the reported heme-related growth defect actually reflects a growth defect for NAD. In the current study hel insertion mutants were constructed and a role for e (P4) in heme acquisition was demonstrated independent of its role in NAD or NMN acquisition. In addition a rat model of infection demonstrated a role for e (P4) in the pathogenesis of invasive disease.

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“…DsbA was demonstrated to be required for pathogenesis of H. influenzae in a mouse model of bacteremia (56). Additionally, the heme-binding lipoprotein HbpA, an important factor required for growth of H. influenzae on several heme sources (26,44), was found to be a substrate of DsbA and was required for pathogenesis. However, the defect of an hbpA mutant was not as severe as that of a dsbA mutant, suggesting that other, unidentified DsbA-dependent factors must be required for pathogenesis.…”

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confidence: 99%

A Novel Zinc Binding System, ZevAB, Is Critical for Survival of Nontypeable Haemophilus influenzae in a Murine Lung Infection Model

et al. 2011

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Nontypeable Haemophilus influenzae (NTHI) is a Gram-negative bacterial pathogen that causes upper and lower respiratory infections. Factors required for pulmonary infection by NTHI are not well understood. Previously, using high-throughput insertion tracking by deep sequencing (HITS), putative lung colonization factors were identified. Also, previous research indicates that secreted disulfide-dependent factors are important for virulence of H. influenzae. In the present study, HITS data were compared with an informatics-based list of putative substrates of the periplasmic oxidoreductase DsbA to find and characterize secreted virulence factors. This analysis resulted in identification of the "zinc binding essential for virulence" (zev) locus consisting of zevA (HI1249) and zevB (HI1248). NTHI mutants of zevA and zevB grew normally in rich medium but were defective for colonization in a mouse lung model. Mutants also exhibited severe growth defects in medium containing EDTA and were rescued by supplementation with zinc. Additionally, purified recombinant ZevA was found to bind to zinc with high affinity. Together, these data demonstrate that zevAB is a novel virulence factor important for zinc utilization of H. influenzae under conditions where zinc is limiting. Furthermore, evidence presented here suggests that zinc limitation is likely an important mechanism for host defense against pathogens during lung infection.

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The heme-binding lipoprotein (HbpA) ofHaemophilus influenzae: Role in heme utilization

Cited by 47 publications

References 32 publications

The haem–haemopexin utilization gene cluster (hxuCBA) as a virulence factor of Haemophilus influenzae

The haem–haemopexin utilization gene cluster (hxuCBA) as a virulence factor of Haemophilus influenzae

Lipoprotein e (P4) of Haemophilus influenzae: role in heme utilization and pathogenesis

A Novel Zinc Binding System, ZevAB, Is Critical for Survival of Nontypeable Haemophilus influenzae in a Murine Lung Infection Model

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