scholarly journals Characterization of igaB, a Second Immunoglobulin A1 Protease Gene in Nontypeable Haemophilus influenzae

2006 ◽  
Vol 74 (10) ◽  
pp. 5860-5870 ◽  
Author(s):  
Matthew M. Fernaays ◽  
Alan J. Lesse ◽  
Xueya Cai ◽  
Timothy F. Murphy
Keyword(s):  
Haemophilus Influenzae ◽  
Virulence Factor ◽  
Protease Activity ◽  
Geographic Origin ◽  
Respiratory Pathogen ◽  
Chronic Obstructive ◽  
Protease Gene ◽  
Nontypeable Haemophilus Influenzae ◽  
Potential Virulence Factor ◽  
Iga1 Protease

ABSTRACT Nontypeable Haemophilus influenzae is an important respiratory pathogen, causing otitis media in children and lower respiratory tract infection in adults with chronic obstructive pulmonary disease (COPD). Immunoglobulin A1 (IgA1) protease is a well-described protein and potential virulence factor in this organism as well as other respiratory pathogens. IgA1 proteases cleave human IgA1, are involved in invasion, and display immunomodulatory effects. We have identified a second IgA1 protease gene, igaB, in H. influenzae that is present in addition to the previously described IgA1 protease gene, iga. Reverse transcriptase PCR and IgA1 protease assays indicated that the gene is transcribed, expressed, and enzymatically active in H. influenzae. The product of this gene is a type 2 IgA1 protease with homology to the iga gene of Neisseria species. Mutants that were deficient in iga, igaB, and both genes were constructed in H. influenzae strain 11P6H, a strain isolated from a patient with COPD who was experiencing an exacerbation. Analysis of these mutants indicated that igaB is the primary mediator of IgA1 protease activity in this strain. IgA1 protease activity assays on 20 clinical isolates indicated that the igaB gene is associated with increased levels of IgA1 protease activity. Approximately one-third of 297 strains of H. influenzae of diverse clinical and geographic origin contained igaB. Significant differences in the prevalence of igaB were observed among isolates from different sites of isolation (sputum > middle ear > nasopharynx). These data support the hypothesis that the newly discovered igaB gene is a potential virulence factor in nontypeable H. influenzae.

scholarly journals Differential Genome Contents of Nontypeable Haemophilus influenzae Strains from Adults with Chronic Obstructive Pulmonary Disease

2006 ◽  
Vol 74 (6) ◽  
pp. 3366-3374 ◽  
Author(s):  
Matthew M. Fernaays ◽  
Alan J. Lesse ◽  
Sanjay Sethi ◽  
Xueya Cai ◽  
Timothy F. Murphy
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Haemophilus Influenzae ◽  
Pulmonary Disease ◽  
Chronic Obstructive ◽  
Protease Gene ◽  
Nontypeable Haemophilus Influenzae ◽  
Bacterial Strains ◽  
Pathogenic Potential ◽  
Obstructive Pulmonary Disease ◽  
Iga Protease

ABSTRACT Haemophilus influenzae is an important cause of otitis media in children and lower respiratory infection in adults with chronic obstructive pulmonary disease (COPD). Patients with COPD experience periodic exacerbations that are associated with acquisition of new bacterial strains. However, not every strain acquisition is associated with exacerbation. To test the hypothesis that genetic differences among strains account for differences in pathogenic potential, a microarray consisting of 4,992 random 1.5- to 3-kb genomic fragments of an exacerbation strain was constructed. Competitive hybridization was performed using six strains associated with exacerbation as well as five strains associated with asymptomatic colonization. Seven sequences that were absent in all five colonization strains and present in at least two exacerbation strains were identified. One such sequence was a previously unreported gene with high homology to the meningococcal immunoglobulin A (IgA) protease gene, which is distinct from the previously described H. influenzae IgA protease. To assess the distribution of the seven sequences among well-characterized strains of H. influenzae, 59 exacerbation strains and 73 asymptomatic colonization strains were screened by PCR for the presence of these sequences. The presence or absence of any single sequence was not significantly associated with exacerbations of COPD. However, logistic regression and subgroup analysis identified combinations of the presence and absence of genes that are associated with exacerbations. These results indicate that patterns of genes are associated with the ability of strains of H. influenzae to cause exacerbations of COPD, supporting the concept that differences in pathogenic potential are based in part on genomic differences among infecting strains, not merely host factors.

scholarly journals Haemophilus influenzae causes cellular trans-differentiation in human bronchial epithelia

2021 ◽  
Vol 27 (3) ◽  
pp. 251-259
Author(s):  
Michael Glöckner ◽  
Sebastian Marwitz ◽  
Kristina Rohmann ◽  
Henrik Watz ◽  
Dörte Nitschkowski ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Haemophilus Influenzae ◽  
Bronchial Epithelium ◽  
Bronchial Epithelial Cells ◽  
Respiratory Pathogen ◽  
Chronic Obstructive ◽  
Bronchial Epithelial ◽  
Extracellular Matrix Components ◽  
The Impact ◽  
Primary Bronchial Epithelial Cells

Non-typeable Haemophilus influenzae (NTHi) is the most common respiratory pathogen in patients with chronic obstructive disease. Limited data is available investigating the impact of NTHi infections on cellular re-differentiation processes in the bronchial mucosa. The aim of this study was to assess the effects of stimulation with NTHi on the bronchial epithelium regarding cellular re-differentiation processes using primary bronchial epithelial cells harvested from infection-free patients undergoing bronchoscopy. The cells were then cultivated using an air-liquid interface and stimulated with NTHi and TGF-β. Markers of epithelial and mesenchymal cells were analyzed using immunofluorescence, Western blot and qRT-PCR. Stimulation with both NTHi and TGF-ß led to a marked increase in the expression of the mesenchymal marker vimentin, while E-cadherin as an epithelial marker maintained a stable expression throughout the experiments. Furthermore, expression of collagen 4 and the matrix-metallopeptidases 2 and 9 were increased after stimulation, while the expression of tissue inhibitors of metallopeptidases was not affected by pathogen stimulation. In this study we show a direct pathogen-induced trans-differentiation of primary bronchial epithelial cells resulting in a co-localization of epithelial and mesenchymal markers and an up-regulation of extracellular matrix components.

scholarly journals Relationship between Azithromycin Susceptibility and Administration Efficacy for Nontypeable Haemophilus influenzae Respiratory Infection

2015 ◽  
Vol 59 (5) ◽  
pp. 2700-2712 ◽  
Author(s):  
Begoña Euba ◽  
Javier Moleres ◽  
Cristina Viadas ◽  
Montserrat Barberán ◽  
Lucía Caballero ◽  
...  
Keyword(s):  
Haemophilus Influenzae ◽  
Respiratory Infection ◽  
Opportunistic Pathogen ◽  
Lavage Fluid ◽  
Cellular Level ◽  
Chronic Obstructive ◽  
Therapeutic Effects ◽  
Nontypeable Haemophilus Influenzae ◽  
Content Type ◽  
Anti Inflammatory

ABSTRACTNontypeableHaemophilus influenzae(NTHI) is an opportunistic pathogen that is an important cause of acute exacerbations of chronic obstructive pulmonary disease (AECOPD). COPD is an inflammatory disease of the airways, and exacerbations are acute inflammatory events superimposed on this background of chronic inflammation. Azithromycin (AZM) is a macrolide antibiotic with antibacterial and anti-inflammatory properties and a clinically proven potential for AECOPD prevention and management. Relationships between AZM efficacy and resistance by NTHI and between bactericidal and immunomodulatory effects on NTHI respiratory infection have not been addressed. In this study, we employed two pathogenic NTHI strains with different AZM susceptibilities (NTHI 375 [AZM susceptible] and NTHI 353 [AZM resistant]) to evaluate the prophylactic and therapeutic effects of AZM on the NTHI-host interplay. At the cellular level, AZM was bactericidal toward intracellular NTHI inside alveolar and bronchial epithelia and alveolar macrophages, and it enhanced NTHI phagocytosis by the latter cell type. These effects correlated with the strain MIC of AZM and the antibiotic dose. Additionally, the effect of AZM on NTHI infection was assessed in a mouse model of pulmonary infection. AZM showed both preventive and therapeutic efficacies by lowering NTHI 375 bacterial counts in lungs and bronchoalveolar lavage fluid (BALF) and by reducing histopathological inflammatory lesions in the upper and lower airways of mice. Conversely, AZM did not reduce bacterial loads in animals infected with NTHI 353, in which case a milder anti-inflammatory effect was also observed. Together, the results of this work link the bactericidal and anti-inflammatory effects of AZM and frame the efficacy of this antibiotic against NTHI respiratory infection.

scholarly journals Draft genome sequence of a nontypeable Haemophilus influenzae strain used in the study of human respiratory infection

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Rajendra KC ◽  
Ronan F. O’Toole
Keyword(s):  
Haemophilus Influenzae ◽  
Genome Sequence ◽  
Draft Genome ◽  
Subsequent Development ◽  
Laboratory Strain ◽  
Draft Genome Sequence ◽  
Chronic Obstructive ◽  
Nontypeable Haemophilus Influenzae ◽  
Obstructive Pulmonary Disease ◽  
Genome Data

Abstract Objectives Nontypeable Haemophilus influenzae (NTHi) is an important human respiratory bacterium that can cause a range of diseases including sinusitis, otitis media, conjunctivitis, pneumonia as well as acute exacerbations of chronic obstructive pulmonary disease (COPD). A number of studies have used NTHi clinical isolate RHH-3 as a laboratory strain for experimentation examining the effect of cigarette smoke and more recently, biomass smoke, on the susceptibility and response of cells lining the respiratory tract to infection. Therefore, definition of the genome content of RHH-3 is required to fully elucidate human-NTHi interactions associated with initial infection and subsequent development of respiratory disease. Data description Here, we present the draft genome sequence of NTHi RHH-3 collected from the sputum of a patient at the Royal Hobart Hospital, Tasmania, Australia. The assembled genome size was 1,839,376 bp consisting of 61 contigs (> 500 bp), with a G+C content of 38.1%. This draft genome data can be accessed at DDBJ/ENA/GenBank under the accession number JADPRR000000000.

scholarly journals Molecular Characterization of Fluoroquinolone Resistance in Nontypeable Haemophilus influenzae Clinical Isolates

2014 ◽  
Vol 59 (1) ◽  
pp. 461-466 ◽  
Author(s):  
Carmen Puig ◽  
José Manuel Tirado-Vélez ◽  
Laura Calatayud ◽  
Fe Tubau ◽  
Junkal Garmendia ◽  
...  
Keyword(s):  
Haemophilus Influenzae ◽  
Nalidixic Acid ◽  
Respiratory Infections ◽  
Pulse Field ◽  
Fluoroquinolone Resistance ◽  
Chronic Obstructive ◽  
Nontypeable Haemophilus Influenzae ◽  
High Genetic Diversity ◽  
Content Type ◽  
Pulse Field Gel Electrophoresis

ABSTRACTNontypeableHaemophilus influenzae(NTHi) is a common cause of respiratory infections in adults, who are frequently treated with fluoroquinolones. The aims of this study were to characterize the genotypes of fluoroquinolone-resistant NTHi isolates and their mechanisms of resistance. Among 7,267H. influenzaeisolates collected from adult patients from 2000 to 2013, 28 (0.39%) were ciprofloxacin resistant according to Clinical and Laboratory Standards Institute (CLSI) criteria. In addition, a nalidixic acid screening during 2010 to 2013 detected five (0.23%) isolates that were ciprofloxacin susceptible but nalidixic acid resistant. Sequencing of their quinolone resistance-determining regions and genotyping by pulse-field gel electrophoresis and multilocus sequence typing of the 25 ciprofloxacin-resistant isolates available and all 5 nalidixic acid-resistant isolates were performed. In the NTHi isolates studied, two mutations producing changes in two GyrA residues (Ser84, Asp88) and/or two ParC residues (Ser84, Glu88) were associated with increased fluoroquinolone MICs. Strains with one or two mutations (n= 15) had ciprofloxacin and levofloxacin MICs of 0.12 to 2 μg/ml, while those with three or more mutations (n= 15) had MICs of 4 to 16 μg/ml. Long persistence of fluoroquinolone-resistant strains was observed in three chronic obstructive pulmonary disease patients. High genetic diversity was observed among fluoroquinolone-resistant NTHi isolates. Although fluoroquinolones are commonly used to treat respiratory infections, the proportion of resistant NTHi isolates remains low. The nalidixic acid disk test is useful for detecting the first changes in GyrA or in GyrA plus ParC among fluoroquinolone-susceptible strains that are at a potential risk for the development of resistance under selective pressure by fluoroquinolone treatment.

scholarly journals Closed Complete Genome Sequences of Two Nontypeable Haemophilus influenzae Strains Containing Novel modA Alleles from the Sputum of Patients with Chronic Obstructive Pulmonary Disease

2018 ◽  
Vol 7 (2) ◽  
Author(s):  
John M. Atack ◽  
Timothy F. Murphy ◽  
Lauren O. Bakaletz ◽  
Kate L. Seib ◽  
Michael P. Jennings
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Haemophilus Influenzae ◽  
Pulmonary Disease ◽  
Complete Genome ◽  
Chronic Obstructive ◽  
Phase Variable ◽  
Nontypeable Haemophilus Influenzae ◽  
Genome Sequences ◽  
Obstructive Pulmonary Disease ◽  
Content Type

Nontypeable Haemophilus influenzae (NTHi) is an important bacterial pathogen that causes otitis media and exacerbations of chronic obstructive pulmonary disease (COPD). Here, we report the complete genome sequences of NTHi strains 10P129H1 and 84P36H1, isolated from COPD patients, which contain the phase-variable epigenetic regulators ModA15 and ModA18, respectively.

Sign in / Sign up

Export Citation Format

Share Document