Adherence of non-typeableHaemophilus influenzaepromotes reorganization of the actin cytoskeleton in human or chinchilla epithelial cellsin vitro

Holmes, Katherine A.

doi:10.1006/mpat.1997.0145

Cited by 25 publications

(26 citation statements)

References 45 publications

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“…We therefore chose the low-passage isolate strain 86-028NP, which was recovered from the nasopharynx of a child with chronic otitis media. This strain has subsequently been well characterized both in vitro (6,46), in chinchilla models of otitis media (5,58,63,111), and partially at the genomic level (72).…”

Section: Methodsmentioning

confidence: 99%

Genomic Sequence of an Otitis Media Isolate of Nontypeable Haemophilus influenzae : Comparative Study with H. influenzae Serotype d, Strain KW20

Harrison¹,

et al. 2005

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In 1995, the Institute for Genomic Research completed the genome sequence of a rough derivative of Haemophilus influenzae serotype d, strain KW20. Although extremely useful in understanding the basic biology of H. influenzae, these data have not provided significant insight into disease caused by nontypeable H. influenzae, as serotype d strains are not pathogens. In contrast, strains of nontypeable H. influenzae are the primary pathogens of chronic and recurrent otitis media in children. In addition, these organisms have an important role in acute otitis media in children as well as other respiratory diseases. Such strains must therefore contain a gene repertoire that differs from that of strain Rd. Elucidation of the differences between these genomes will thus provide insight into the pathogenic mechanisms of nontypeable H. influenzae. The genome of a representative nontypeable H. influenzae strain, 86-028NP, isolated from a patient with chronic otitis media was therefore sequenced and annotated. Despite large regions of synteny with the strain Rd genome, there are large rearrangements in strain 86-028NP's genome architecture relative to the strain Rd genome. A genomic island similar to an island originally identified in H. influenzae type b is present in the strain 86-028NP genome, while the mu-like phage present in the strain Rd genome is absent from the strain 86-028NP genome. Two hundred eighty open reading frames were identified in the strain 86-028NP genome that were absent from the strain Rd genome. These data provide new insight that complements and extends the ongoing analysis of nontypeable H. influenzae virulence determinants.In 1995 Haemophilus influenzae strain Rd, a rough derivative of H. influenzae serotype d strain KW20 (strain Rd hereafter), became the first free-living organism to have its genome sequenced to completion (34). Importantly, this also helped establish the large-scale shotgun approach, mated with the utilization of a scaffolding library and computer-assisted assembly, as a rational and expeditious approach for the sequencing of small bacterial genomes. Strain Rd was chosen as the prototypic bacterium for complete genome sequencing as it has a genome size representative of other bacteria and a GϩC content close to that of the human genome. Additionally, at the time of sequencing, a physical map of the strain Rd genome did not exist, so this genome was a good test for the approach of shotgun sequencing, scaffolding, and assembly (34).Although strain Rd is the exemplar organism for the current small-genome sequencing rationale and an important model organism for studying H. influenzae biology, strain Rd is a poor model for the study of pathogenicity caused by members of the genus Haemophilus. Serotype b strains of H. influenzae cause invasive diseases, for example, meningitis, and nontypeable H. influenzae (NTHi) strains principally have a role in localized respiratory disease, particularly in otitis media, acute sinusitis, and community-acquired pneumonia and have important conseque...

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Section: Methodsmentioning

confidence: 99%

Genomic Sequence of an Otitis Media Isolate of Nontypeable Haemophilus influenzae : Comparative Study with H. influenzae Serotype d, Strain KW20

Harrison¹,

et al. 2005

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“…NTHi strain 86-028NP was recovered from the nasopharynx of a child with chronic otitis media. This strain has been well characterized both in vitro (8,32) and in chinchilla models of OM (7,47,81). The genome sequence has been published (29).…”

Section: Methodsmentioning

confidence: 99%

The OxyR Regulon in Nontypeable Haemophilus influenzae

et al. 2007

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Nontypeable Haemophilus influenzae (NTHi) is a gram-negative bacterium and a common commensal organism of the upper respiratory tract in humans. NTHi causes a number of diseases, including otitis media, sinusitis, conjunctivitis, exacerbations of chronic obstructive pulmonary disease, and bronchitis. During the course of colonization and infection, NTHi must withstand oxidative stress generated by insult due to multiple reactive oxygen species produced endogenously by other copathogens and by host cells. Using an NTHi-specific microarray containing oligonucleotides representing the 1821 open reading frames of the recently sequenced NTHi isolate 86-028NP, we have identified 40 genes in strain 86-028NP that are upregulated after induction of oxidative stress due to hydrogen peroxide. Further comparisons between the parent and an isogenic oxyR mutant identified a subset of 11 genes that were transcriptionally regulated by OxyR, a global regulator of oxidative stress. Interestingly, hydrogen peroxide induced the OxyR-independent upregulation of expression of the genes encoding components of multiple iron utilization systems. This finding suggested that careful balancing of levels of intracellular iron was important for minimizing the effects of oxidative stress during NTHi colonization and infection and that there are additional regulatory pathways involved in iron utilization.In the evolution of life, a delicate physiological balance has arisen to compensate for both an organism's need for oxygen and the attendant lethal consequences of oxygen's toxicity. For example, in the electron transport chain, electrons can be inadvertently transferred from redox-active proteins to oxygen, producing reactive oxygen species (ROS) such as superoxide and hydrogen peroxide (H 2 O 2 ). The effects of ROS on cells can then be exacerbated by the presence of free iron which, via the Fenton reaction, can react with H 2 O 2 to produce more highly reactive hydroxyl radicals (34, 40, 52). Within a host, this problem is compounded by the release of extracellular ROS by phagocytes, which again, can have deleterious effects on invading pathogens (13). Thus, bacteria have evolved an array of increasingly well-defined mechanisms to abrogate the effects of oxidative stress. Proteins involved in such processes include catalase, which decomposes H 2 O 2 , and members of both the AhpCF/TsaA family of alkylhydroperoxidases and the organic hydroperoxide resistance proteins (Ohr) that decompose organic peroxides. Also, DNA-binding ferritin-like proteins (Dps) sequester free iron and bind to DNA, thus protecting DNA from damage (27,33,45,53,59,60,67). In addition, many bacterial species possess genes encoding OxyR, a global regulator of antioxidant defenses (24, 66).Protection against oxidative stress is especially important to nontypeable Haemophilus influenzae (NTHi). NTHi is one of three bacterial commensal organisms, the others being Streptococcus pneumoniae and Moraxella catarrhalis, which can ascend a virus-compromised eustachian tube and caus...

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“…We therefore chose the low-passage-number isolates, strains 1885MEE and 86-028NP, that were independently recovered from children with chronic OM. Both have subsequently been well characterized in vitro (3,24) as well as in chinchilla models of OM, with strain 86-028NP being the better understood (2,14,48).…”

Section: Methodsmentioning

confidence: 99%

Partial Analysis of the Genomes of Two Nontypeable Haemophilus influenzae Otitis Media Isolates

et al. 2004

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In 1995, The Institute for Genomic Research completed the genomic sequence of a rough derivative of Haemophilus influenzae serotype d, strain KW20. This sequence, though extremely useful in understanding the basic biology of H. influenzae, has yet to provide significant insight into our understanding of disease caused by nontypeable H. influenzae (NTHI), because serotype d strains are not generally pathogens. In contrast, NTHI strains are frequently mucosal pathogens and are the primary pathogens of chronic otitis media as well as a significant cause of acute otitis media in children. Thus, it is of great importance to further understand their biology. We used a DNA-based microarray approach to identify genes present in a clinical isolate of NTHI that were absent from strain Rd. We also sequenced the genome of a second NTHI isolate from a child with chronic otitis media to threefold coverage and then used an array of bioinformatics tools to identify genes present in this NTHI strain but absent from strain Rd. These methods were complementary in approach and results. We identified, in both strains, homologues of H. influenzae lav, an autotransported protein of unknown function; tnaA, which encodes tryptophanase; as well as a homologue of Pasteurella multocida tsaA, which encodes an alkyl peroxidase that may play a role in protection against reactive oxygen species. We also identified a number of putative restriction-modification systems, bacteriophage genes and transposon-related genes. These data provide new insight that complements and extends our ongoing analysis of NTHI virulence determinants.

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Adherence of non-typeableHaemophilus influenzaepromotes reorganization of the actin cytoskeleton in human or chinchilla epithelial cellsin vitro

Cited by 25 publications

References 45 publications

Genomic Sequence of an Otitis Media Isolate of Nontypeable Haemophilus influenzae : Comparative Study with H. influenzae Serotype d, Strain KW20

Genomic Sequence of an Otitis Media Isolate of Nontypeable Haemophilus influenzae : Comparative Study with H. influenzae Serotype d, Strain KW20

The OxyR Regulon in Nontypeable Haemophilus influenzae

Partial Analysis of the Genomes of Two Nontypeable Haemophilus influenzae Otitis Media Isolates

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