Determination of Inherited Traits of H. Influenzae by Desoxyribonucleic Acid Fractions Isolated From Type-Specific Cells

Alexander, Hattie E.; Leidy, Grace

doi:10.1084/jem.93.4.345

Cited by 150 publications

(57 citation statements)

References 8 publications

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“…NTHi strain 86-028NP is a minimally passaged clinical isolate from a patient who underwent tympanostomy and tube insertion for chronic OM (Suzuki & Bakaletz, 1994). H. influenzae strain Rd KW20 was originally isolated over 60 years ago (Alexander & Leidy, 1951) and its genome was sequenced in 1995 (Fleischmann et al, 1995). Isolates of H. influenzae were routinely maintained on chocolate agar with bacitracin at 37 uC.…”

Section: Methodsmentioning

confidence: 99%

“…With respect to haem utilization, the Rd tehB mutant was marginally impaired in haem utilization and thus the effect of complementation was difficult to discern. This difference likely reflects the genetic differences between the pathogenic, clinically isolated, type b isolate 10810 and the multiply passaged Rd KW20 isolate, which was originally isolated over 60 years ago (Alexander & Leidy, 1951).…”

Section: Role Of Tehb In Resistance To Tellurite and Oxidationmentioning

confidence: 99%

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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%

Section: Role Of Tehb In Resistance To Tellurite and Oxidationmentioning

confidence: 99%

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

et al. 2010

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“…Following internalization, the DNA can be inserted into the chromosome by homologous recombination. While Hi isolates are competent and can be readily transformed in the laboratory environment (Alexander & Leidy, 1951), the contribution of homologous recombination to population structure in nature is less clear. One phylogenetic study (Feil et al, 2001) found relatively high congruence between housekeeping loci, suggesting that homologous recombination was not frequent enough to scramble phylogenetic signals.…”

Section: Introductionmentioning

confidence: 99%

Population subdivision and the detection of recombination in non-typable Haemophilus influenzae

2012

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The disparity in diversity between unencapsulated (non-typable; NT) and encapsulated, serotypable Haemophilus influenzae (Hi) has been recognized for some time. It has previously been suggested that the wider diversity evidenced within NTHi compared with typable lineages may be due to different rates of recombination within the encapsulated and NT populations. To examine whether there is evidence for different levels of recombination within typable and NT lineages of Hi, we performed a statistical genetic analysis of 819 distinct genotypes of Hi to explore the congruence of serotype with population genetic clustering, and to identify patterns of recombination within the Hi population. We find that a significantly larger proportion of NT isolates show evidence of recombination, compared with typable isolates, and also that when admixture is present, the total amount of recombination per strain is greater within NT isolates, compared with the typable population. Furthermore, we demonstrate significant heterogeneity in the number of admixed individuals between NT lineages themselves, while such variation was not observed in typable lineages. This variability suggests that factors other than the presence of capsule are important determinants of recombination rate in the Hi population. INTRODUCTIONHaemophilus influenzae (Hi) is a Gram-negative bacterium commonly isolated from episodes of asymptomatic nasopharyngeal carriage. While the vast majority of Hi exists in carriage rather than disease states, it remains a globally significant pathogen, capable of causing both localized mucosal infections, such as otitis media, and invasive infections, such as meningitis and septicaemia (Turk, 1984). Hi is thought to cause at least three million cases of serious illness every year, mostly in young children (WHO, 2005). To date, six distinct serotypes (designated a-f) of Hi are distinguishable (Pittman, 1930), while a substantial proportion of the population is unencapsulated and so remains non-typable (NT). Of the encapsulated population, serotype b has historically been the most significant pathogen, and is responsible for approximately 95 % of all invasive Hi disease in unvaccinated children (Falla et al., 1993;Peltola, 2000). An effective vaccine against H. influenzae serotype b (Hib) disease has been available since the early 1980s (Anderson, 1983;Chu et al., 1983), and its introduction into childhood immunization programs in the developed world has all but eliminated Hib disease in western countries (for example, see Bisgard et al., 1998;Booy et al., 1997). However, vaccination is rare in many developing countries, where Hib remains a significant cause of mortality, causing an estimated 380 000 deaths each year (WHO, 2005).While Hib disease is controlled by vaccination in the developed world, Hi possessing the other serotypes, as well as NTHi, are also reported to be capable of causing invasive disease (St Geme, 1993;Tsang et al., 2007; WaggonerFountain et al., 1995). NTHi is also a leading cause of economically signific...

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“…From the genetic point of view the most typical aspect of recombination in this strain is that exchange of some genetically determined characters involves, a t the same time, the exchange of other physiologically unrelated characters with a high probability. Moreover, whole cells have so far been found necessary for recombination to occur, in contrast with transformations or genetic transfers in other bacterial species, such as pneumococcus (Avery, MacLeod & McCarty, 1944 ;Griffith, 1928 ;Hotchkiss, 1951), HaemophiZus (Alexander & Leidy, 1951 ) and Salmonella typhimuriuin (Zinder & Lederberg, 1952), which have been demonstrated by means of cell-free preparations. Thus, transfer of genetic material in Bact.…”

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confidence: 99%

An Infective Factor Controlling Sex Compatibility in Bacterium coli

1953

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Determination of Inherited Traits of H. Influenzae by Desoxyribonucleic Acid Fractions Isolated From Type-Specific Cells

Cited by 150 publications

References 8 publications

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

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

Population subdivision and the detection of recombination in non-typable Haemophilus influenzae

An Infective Factor Controlling Sex Compatibility in Bacterium coli

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