Characterisation of invasive clinical<i>Haemophilus influenzae</i>isolates in Queensland, Australia using whole-genome sequencing

Staples, Megan; Graham, Rikki; Jennison, Amy V.

doi:10.1017/s0950268817000450

Cited by 22 publications

(27 citation statements)

References 37 publications

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“…Because all the subjects in this study had COPD for years prior to being sampled for NTHi, we could not conclude that null alleles of fadL arose within COPD patient lungs, despite 6 of 20 multi-isolate CTs being polymorphic for null alleles, since these might also arise in the normal commensal population of NTHi in the nasopharynx. To test whether loss of fadL function was specifically associated with lower airway infections, we first examined the distribution of full-length and truncated fadL alleles across 181 publicly available genomes (excluding those from the Pettigrew et al study [ 36 ]) derived from isolates with diverse clinical origins ( 26 , 66 , 67 ) ( Fig. S4 ).…”

Section: Resultsmentioning

confidence: 99%

Antagonistic Pleiotropy in the Bifunctional Surface Protein FadL (OmpP1) during Adaptation of Haemophilus influenzae to Chronic Lung Infection Associated with Chronic Obstructive Pulmonary Disease

Moleres

Fernández-Calvet

Ehrlich

et al. 2018

mBio

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Nontypeable Haemophilus influenzae is an important pathogen in patients with chronic obstructive pulmonary disease (COPD). To elucidate the bacterial pathways undergoing in vivo evolutionary adaptation, we compared bacterial genomes collected over time from 13 COPD patients and identified recurrent genetic changes arising in independent bacterial lineages colonizing different patients. Besides finding changes in phase-variable genes, we found recurrent loss-of-function mutations in the ompP1 (fadL) gene. We show that loss of OmpP1/FadL function reduces this bacterium’s ability to infect cells via the hCEACAM1 epithelial receptor but also increases its resistance to bactericidal fatty acids enriched within the COPD lung, suggesting a case of antagonistic pleiotropy that restricts ΔfadL strains’ niche. These results show how H. influenzae adapts to host-generated inflammatory mediators in the COPD airways.

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Section: Resultsmentioning

confidence: 99%

Antagonistic Pleiotropy in the Bifunctional Surface Protein FadL (OmpP1) during Adaptation of Haemophilus influenzae to Chronic Lung Infection Associated with Chronic Obstructive Pulmonary Disease

Moleres

Fernández-Calvet

Ehrlich

et al. 2018

mBio

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“…Among 18 BLNAR NTHis collected in Spain, 15 different genetically diverse STs were identified . Unlike high genetic variability of NTHis, encapsulated isolates express widely clonal characteristics . The high heterogeneity of NTHis is a block to the development of vaccines and may also be the reason for rare outbreaks of NTHi infections worldwide.…”

Section: Discussionmentioning

confidence: 99%

Widespread of non‐typeable Haemophilus influenzae with high genetic diversity after two decades use of Hib vaccine in China

Dong

Shi

Cheng

et al. 2019

Clinical Laboratory Analysis

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This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. AbstractBackground: The aim of this study was to analyze the microbiological characteristics of nasopharyngeal carriage Haemophilus influenzae isolates collected from children with respiratory infections in Beijing hospital and Youyang Hospital of China. Methods:The serotypes of all isolates were determined using latex agglutinated antisera (a-f). The minimum inhibitory concentrations (MICs) of 11 antibiotics were determined using E-test strips. For the beta-lactamase-negative ampicillin-resistant (BLNAR) isolates, ftsI gene was sequenced based on fragments amplified by PCR. STs of H influenzae isolates were determined by multi-locus sequence typing. Results:The overall carriage rate of H influenzae in the study population was 9.1% (362/3984). One hundred and ninety H influenzae isolates which were selected in our study were non-typeable (NTHi) and 44 (23.2%) of them were positive for β-lactamase.All isolates were susceptible to ceftriaxone and levofloxacin. Susceptibility rates to erythromycin and sulfamethoxazole-trimethoprim in Beijing were significantly higher than Youyang (P < .05). Thirty-six BLNAR isolates were identified. The MLST analysis showed 108 STs in 190 isolates, the most common of which were ST408 (11, 5.8%), ST914 (10, 5.3%), ST57 (9, 4.7%), and ST834 (6, 3.2%). Twelve STs were detected in both of the study sites, which covered 63 isolates. Conclusions:All isolates in the present study were NTHi, which suggested widespread of this type in China. The BLNAR isolates were detected more frequently than before. Because high genetic diversity of NTHi isolates of H influenzae exists worldwide, it is important to continuously monitor these bacteria in the future.

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“…hicap implementation and validation 43 hicap uses a reference database to identify genes expected in the six cap loci (cap-a to cap-f). To this 44 end, a curated nucleotide sequence database of cap locus genes was constructed by extracting the 45 protein-coding sequences annotated from cap loci in publicly available sequences of well defined H. 46 influenzae serotypes (Table 1).…”

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confidence: 99%

hicap:in silicoserotyping of theHaemophilus influenzaecapsule locus

Watts

Holt

2019

Preprint

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Haemophilus influenzae exclusively colonises the human nasopharynx and can cause a variety of respiratory infections as well as invasive diseases including meningitis and sepsis. A key virulence determinant of H. influenzae is the polysaccharide capsule of which six serotypes are known, each encoded by a distinct variation of the capsule biosynthesis locus (cap-a to cap-f). H. influenzae type b (Hib) was historically responsible for the majority of invasive H. influenzae disease and prevalence has been markedly reduced in countries that have implemented vaccination programs targeting this serotype. In the postvaccine era, non-typeable H. influenzae emerged as the most dominant group causing disease but in recent years a resurgence of encapsulated H. influenzae strains has also been observed, most notably serotype a. Given the increasing incidence of encapsulated strains and the high frequency of Hib in countries without vaccination programs, there is growing interest in genomic epidemiology of H. influenzae. Here we present hicap, a software tool for rapid in silico serotype prediction from H. influenzae genome sequences. hicap is written using Python3 and is freely available at https://github.com/scwatts/hicap under the GPL3 license. To demonstrate the utility of hicap, we used it to investigate the cap locus diversity and distribution in 691 high-quality H. influenzae genomes from GenBank. These analyses identified cap loci in 95 genomes and confirmed the general association of each serotype with a unique clonal lineage and also identified occasional recombination between lineages giving rise to hybrid cap loci (2% of encapsulated strains). 7 non-typeable H. influenzae (NTHi) [2]. 8Biosynthesis of the polysaccharide capsule is controlled by the cap loci (cap-a to cap-f), which 9 each include three contiguous but functionally distinct regions (I, II, and III) ( Figure 1). Regions I 10 and III are common to all six cap loci, and are associated with cellular transport (bex operon, region 11

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Characterisation of invasive clinicalHaemophilus influenzaeisolates in Queensland, Australia using whole-genome sequencing

Cited by 22 publications

References 37 publications

Antagonistic Pleiotropy in the Bifunctional Surface Protein FadL (OmpP1) during Adaptation of Haemophilus influenzae to Chronic Lung Infection Associated with Chronic Obstructive Pulmonary Disease

Antagonistic Pleiotropy in the Bifunctional Surface Protein FadL (OmpP1) during Adaptation of Haemophilus influenzae to Chronic Lung Infection Associated with Chronic Obstructive Pulmonary Disease

Widespread of non‐typeable Haemophilus influenzae with high genetic diversity after two decades use of Hib vaccine in China

hicap:in silicoserotyping of theHaemophilus influenzaecapsule locus

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