Patients with Chronic Obstructive Pulmonary Disease harbour a variation of Haemophilus species

Osman, Karen L.; Jefferies, Johanna M.C.; Woelk, Christopher H.; Devos, Nathalie; Pascal, Thierry; Mortier, Marie-Cécile; Devaster, Jeanne-Marie; Wilkinson, Tom; Cleary, David W.; Clarke, Stuart C.

doi:10.1038/s41598-018-32973-3

Cited by 14 publications

(10 citation statements)

References 52 publications

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“…NTHi strains ST14, ST408 and ST201 isolated from COPD patients undergoing bronchoscopy ( Osman et al, 2018 , Wallington et al, 2018 ), and NTHi-GFP-375 SR (kindly gifted by Dr. Derek Hood, MRC Harwell, UK) ( Mulay et al, 2016 ) were grown as previously described ( Kirkham et al, 2013 ). Briefly, NTHi was cultured from frozen stock on to chocolate blood agar plates (CHOC, Oxoid, Basingstoke, UK) and incubated overnight at 37°C, 5% CO 2 .…”

Section: Methodsmentioning

confidence: 99%

Dual RNASeq Reveals NTHi-Macrophage Transcriptomic Changes During Intracellular Persistence

Ackland

Heinson

Cleary

et al. 2021

Front. Cell. Infect. Microbiol.

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Nontypeable Haemophilus influenzae (NTHi) is a pathobiont which chronically colonises the airway of individuals with chronic respiratory disease and is associated with poor clinical outcomes. It is unclear how NTHi persists in the airway, however accumulating evidence suggests that NTHi can invade and persist within macrophages. To better understand the mechanisms of NTHi persistence within macrophages, we developed an in vitro model of NTHi intracellular persistence using human monocyte-derived macrophages (MDM). Dual RNA Sequencing was used to assess MDM and NTHi transcriptomic regulation occurring simultaneously during NTHi persistence. Analysis of the macrophage response to NTHi identified temporally regulated transcriptomic profiles, with a specific ‘core’ profile displaying conserved expression of genes across time points. Gene list enrichment analysis identified enrichment of immune responses in the core gene set, with KEGG pathway analysis revealing specific enrichment of intracellular immune response pathways. NTHi persistence was facilitated by modulation of bacterial metabolic, stress response and ribosome pathways. Levels of NTHi genes bioC, mepM and dps were differentially expressed by intracellular NTHi compared to planktonic NTHi, indicating that the transcriptomic adaption was distinct between the two different NTHi lifestyles. Overall, this study provides crucial insights into the transcriptomic adaptations facilitating NTHi persistence within macrophages. Targeting these reported pathways with novel therapeutics to reduce NTHi burden in the airway could be an effective treatment strategy given the current antimicrobial resistance crisis and lack of NTHi vaccines.

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Section: Methodsmentioning

confidence: 99%

Dual RNASeq Reveals NTHi-Macrophage Transcriptomic Changes During Intracellular Persistence

Ackland

Heinson

Cleary

et al. 2021

Front. Cell. Infect. Microbiol.

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“…Moreover, current data show a significantly higher abundance of taxa belonging to the genera Haemophilus, Stenotrophomonas, and Enterobacteriaceae family in the ILD group, whereas Corynebacterium and Neisseria are more abundant in the sarcoidosis group. However, Haemophilus , known as pathogenic-bacteria, is usually observed in COPD patients 30 .…”

Section: Discussionmentioning

confidence: 99%

Comparative analysis of the alveolar microbiome in COPD, ECOPD, Sarcoidosis, and ILD patients to identify respiratory illnesses specific microbial signatures

Gupta

Shariff

Chaturvedi

et al. 2021

Sci Rep

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Studying respiratory illness-specific microbial signatures and their interaction with other micro-residents could provide a better understanding of lung microbial ecology. Each respiratory illness has a specific disease etiology, however, so far no study has revealed disease—specific microbial markers. The present study was designed to determine disease-specific microbial features and their interactions with other residents in chronic obstructive pulmonary diseases (stable and exacerbated), sarcoidosis, and interstitial lung diseases. Broncho-alveolar lavage samples (n = 43) were analyzed by SSU rRNA gene sequencing to study the alveolar microbiome in these diseases. A predominance of Proteobacteria followed by Firmicutes, Bacteroidetes, Actinobacteria, and Fusobacteria was observed in all the disease subsets. Shannon diversity was significantly higher in stable COPD when compared to exacerbated chronic obstructive pulmonary disease (ECOPD) (p = 0.0061), and ILD patient samples (p = 0.037). The lung microbiome of the patients with stable COPD was more diverse in comparison to ECOPD and ILD patients (p < 0.001). Lefse analysis identified 40 disease—differentiating microbial features (LDA score (log10) > 4). Species network analysis indicated a significant correlation (p < 0.05) of diseases specific microbial signature with other lung microbiome members. The current study strengthens the proposed hypothesis that each respiratory illness has unique microbial signatures. These microbial signatures could be used as diagnostic markers to differentiate among various respiratory illnesses.

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“…An absence of Hi was assumed to indicate H. haemolyticus presence, based on previous observations published by Murphy et al [ 20 ]. Haemophilus species was further assessed by whole genome sequencing and additional markers analysis, including the presence/absence of the lgtC gene and copper-zinc superoxide dismutase ( sodC ) gene, to confirm the presence of H. haemolyticus , as described by Osman et al [ 21 ].…”

Section: Methodsmentioning

confidence: 99%

Sputum sample positivity for Haemophilus influenzae or Moraxella catarrhalis in acute exacerbations of chronic obstructive pulmonary disease: evaluation of association with positivity at earlier stable disease timepoints

Malvisi¹,

Taddei²,

Yarraguntla³

et al. 2021

Respir Res

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Background Infection with Haemophilus influenzae (Hi) or Moraxella catarrhalis (Mcat) is a risk factor for exacerbation in chronic obstructive pulmonary disease (COPD). The ability to predict Hi- or Mcat-associated exacerbations may be useful for interventions developed to reduce exacerbation frequency. Methods In a COPD observational study, sputum samples were collected at monthly stable-state visits and at exacerbation during two years of follow-up. Bacterial species (Hi, Mcat) were identified by culture and quantitative PCR assay. Post-hoc analyses were conducted to assess: (1) first Hi- or Mcat-positive exacerbations given presence or absence of Hi or Mcat at the screening visit (stable-state timepoint); (2) first Hi- or Mcat-positive exacerbations given presence or absence of Hi or Mcat at stable timepoints within previous 90 days; (3) second Hi- or Mcat-positive exacerbations given presence or absence of Hi or Mcat at stable timepoints within previous 90 days. Percentages and risk ratios (RRs) with 95% confidence intervals were calculated. Results PCR results for analyses 1, 2 and 3 (samples from 84, 88 and 83 subjects, respectively) showed that the risk of an Hi- or Mcat-positive exacerbation is significantly higher if sputum sample was Hi- or Mcat-positive than if Hi- or Mcat-negative at previous stable timepoints (apart from Mcat in analysis 3); RRs ranged from 2.1 to 3.2 for Hi and 1.9 to 2.6 for Mcat.For all analyses, the percentage of Hi- or Mcat-positive exacerbations given previous Hi- or Mcat-positive stable timepoints was higher than the percentage of Hi- or Mcat-positive exacerbations if Hi- or Mcat-negative at previous stable timepoints. Percentage of Hi- or Mcat-positive exacerbations given previous Hi- or Mcat-negative stable timepoints was 26.3%–37.0% for Hi and 17.6%–19.7% for Mcat. Conclusions Presence of Hi or Mcat at a stable timepoint was associated with a higher risk of a subsequent Hi- or Mcat-associated exacerbation compared with earlier absence. However, a large percentage of Hi- or Mcat-associated exacerbations was not associated with Hi/Mcat detection at an earlier timepoint. This suggests that administration of an intervention to reduce these exacerbations should be independent of bacterial presence at baseline. Trial Registrationhttps://clinicaltrials.gov/; NCT01360398, registered May 25, 2011

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Patients with Chronic Obstructive Pulmonary Disease harbour a variation of Haemophilus species

Cited by 14 publications

References 52 publications

Dual RNASeq Reveals NTHi-Macrophage Transcriptomic Changes During Intracellular Persistence

Dual RNASeq Reveals NTHi-Macrophage Transcriptomic Changes During Intracellular Persistence

Comparative analysis of the alveolar microbiome in COPD, ECOPD, Sarcoidosis, and ILD patients to identify respiratory illnesses specific microbial signatures

Sputum sample positivity for Haemophilus influenzae or Moraxella catarrhalis in acute exacerbations of chronic obstructive pulmonary disease: evaluation of association with positivity at earlier stable disease timepoints

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