Transcriptional Profile of
            <i>Haemophilus influenzae</i>
            : Effects of Iron and Heme

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

doi:10.1128/jb.00417-06

Cited by 34 publications

(55 citation statements)

References 31 publications

(19 reference statements)

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“…To determine the impact of Fe/Hm levels on transcription of tehB in NTHi strains R2846 and 86-028NP the transcriptional regulation experiment detailed by Whitby et al (2006a) was repeated with these isolates. To determine the response of Hib strain 10810 to tellurite or oxidative stress, we examined the transcription of the gene before and after addition of a sublethal dose of tellurite or cumene hydroperoxide.…”

Section: Methodsmentioning

confidence: 99%

Characterization of the Haemophilus influenzae tehB gene and its role in virulence

et al. 2010

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The Haemophilus influenzae ORF designated HI1275 in the Rd KW20 genomic sequence encodes a putative S-adenosyl methyltransferase with significant similarity to tellurite-resistance determinants (tehB) in other species. While the H. influenzae tehB can complement an Escherichia coli tehB mutation, thus restoring tellurite resistance, its role in H. influenzae is unknown. In a previous study defining the iron and haem modulon of H. influenzae, we showed that transcription of this gene in H. influenzae Rd KW20 increases during growth in iron-and haem-restricted media. Since iron and haem uptake genes, and other known virulence factors, constitute the majority of the iron-and haem-regulated gene set, we postulated that tehB may play a role in nutrient acquisition and/or the virulence of H. influenzae. A tehB mutant was constructed in the H. influenzae type b strain 10810 and was evaluated for growth defects in various supplemented media, as well as for its ability to cause infection in rat models of infection. Deletion of tehB leads to an increase in sensitivity both to tellurite and to the oxidizing agents cumene hydroperoxide, tert-butyl hydroperoxide and hydrogen peroxide. The tehB mutant additionally showed a significantly reduced ability to utilize free haem as well as several haem-containing moieties including haem-human serum albumin, haemoglobin and haemoglobin-haptoglobin. Examination of the regulation kinetics indicated that transcription of tehB was independent of both tellurite exposure and oxidative stress. Paired comparisons of the tehB mutant and the wild-type H. influenzae strain 10810 showed that tehB is required for wild-type levels of infection in rat models of H. influenzae invasive disease. To our knowledge this is the first report of a role for tehB in virulence in any bacterial species. These data demonstrate that H. influenzae tehB plays a role in both resistance to oxidative damage and haem uptake/utilization, protects H. influenzae from tellurite exposure, and is important for virulence of this organism in an animal model of invasive disease.

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Section: Methodsmentioning

confidence: 99%

Characterization of the Haemophilus influenzae tehB gene and its role in virulence

et al. 2010

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“…2C). Transcriptome analysis has also identified additional genes that are activated by iron-bound Fur (12,56,68,101,102,107).…”

Section: Fur Functions As a Global Regulatory Proteinmentioning

confidence: 99%

“…Recently, global analyses of iron-and/or Fur-responsive transcriptomes of diverse bacterial pathogens, such as H. pylori, Pseudomonas syringae, Vibrio cholerae, Yersinia pestis, Haemophilus influenzae, S. enterica serovar Typhimurium, and Listeria monocytogenes, have revealed a number of novel regulatory roles for Fur (12,20,40,56,68,94,101,102,107). First, Fur has been demonstrated to repress transcription even in the absence of iron, a process termed apo-Fur regulation (13) (Fig.…”

Section: Fur Functions As a Global Regulatory Proteinmentioning

confidence: 99%

Fur-Mediated Global Regulatory Circuits in Pathogenic Neisseria Species

Genco

2012

J Bacteriol

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“…Protein F (also annotated as a Y. pestis yfeA homologue) has been identified amongst other H. influenzae proteins to be upregulated during physiological conditions [40,41]. Culturing NTHi in sputum obtained from COPD-patients resulted in a 3.9-fold increase in PF concentration.…”

Section: Pathogens Such As S Pneumoniae S Pyogenes Moraxella Catmentioning

confidence: 99%