Insights into the population structure and pan-genome of Haemophilus influenzae

Pinto, Miguel; González-Díaz, Aida; Machado, Miguel P.; Duarte, Sílvia; Vieira, Luı́s; Carriço, João André; Martí, Sara; Bajanca-Lavado, Paula; Gomes, João Paulo

doi:10.1016/j.meegid.2018.10.025

Cited by 40 publications

(66 citation statements)

References 81 publications

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“…H. influenzae , and particularly NTHi, have enormous genetic diversity due to their intrinsic transformability and the high rate of recombination with exogenous DNA from their environment (Mell, Shumilina, Hall, & Redfield, ), such that less than 50% of ORFs are present in all strains (the core genome) while the remainder are present variably and represent an accessory genome (De Chiara et al, ; Garmendia, Marti‐Lliteras, Moleres, Puig, & Bengoechea, ). In a group of 88 H. influenzae genome assemblies (NTHi and Hib) (Pinto et al, ), 100% of strains have genes for the outer membrane heme transporters, hup (Morton et al, ) and hemR (Bracken, Baer, Abdur‐Rashid, Helms, & Stojiljkovic, ), as well as the hxuCBA genes for heme uptake from hemopexin (Cope et al, ) (Supplementary Table ). In addition, 98% of strains have at least 1 gene encoding a transporter for heme uptake from hemoglobin/haptoglobin ( hgpA, hgpB, hgpC ; (Jin et al, , Morton et al, , Ren et al, )).…”

Section: Discussionmentioning

confidence: 99%

A heme‐binding protein produced by Haemophilus haemolyticus inhibits non‐typeable Haemophilus influenzae

Latham

Torrado

Atto

et al. 2019

Molecular Microbiology

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Commensal bacteria serve as an important line of defense against colonisation by opportunisitic pathogens, but the underlying molecular mechanisms remain poorly explored. Here, we show that strains of a commensal bacterium, Haemophilus haemolyticus, make hemophilin, a heme‐binding protein that inhibits growth of the opportunistic pathogen, non‐typeable Haemophilus influenzae (NTHi) in culture. We purified the NTHi‐inhibitory protein from H. haemolyticus and identified the hemophilin gene using proteomics and a gene knockout. An x‐ray crystal structure of recombinant hemophilin shows that the protein does not belong to any of the known heme‐binding protein folds, suggesting that it evolved independently. Biochemical characterisation shows that heme can be captured in the ferrous or ferric state, and with a variety of small heme‐ligands bound, suggesting that hemophilin could function under a range of physiological conditions. Hemophilin knockout bacteria show a limited capacity to utilise free heme for growth. Our data suggest that hemophilin is a hemophore and that inhibition of NTHi occurs by heme starvation, raising the possibility that competition from hemophilin‐producing H. haemolyticus could antagonise NTHi colonisation in the respiratory tract.

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Section: Discussionmentioning

confidence: 99%

A heme‐binding protein produced by Haemophilus haemolyticus inhibits non‐typeable Haemophilus influenzae

Latham

Torrado

Atto

et al. 2019

Molecular Microbiology

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“…Characterization of the capsule genes from WGS data enabled the development of an in silico method for accurately predicting the serotype, which was highly concordant with SAST and rt-PCR. Two other WGS methods for determining the Hi serotype have been recently described [14, 33]. However, this is the first comprehensive characterization of the capsule locus using a large isolate collection that includes a comparative analysis of all three serotyping methods.…”

Section: Discussionmentioning

confidence: 99%

“…Two main groups were identified: Group I contained isolates from NTHi and serotypes Hia, Hib, Hic, and Hid, while Group II contained Hia, Hie and Hif isolates [9–11]. More recently, WGS studies confirmed that NTHi isolates were more diverse, with multiple phylogenetic clades detected [12–14].…”

Section: Introductionmentioning

confidence: 99%

Genomic characterization of Haemophilus influenzae: a focus on the capsule locus

et al. 2019

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Background Haemophilus influenzae (Hi) can cause invasive diseases such as meningitis, pneumonia, or sepsis. Typeable Hi includes six serotypes (a through f), each expressing a unique capsular polysaccharide. The capsule, encoded by the genes within the capsule locus, is a major virulence factor of typeable Hi. Non-typeable (NTHi) does not express capsule and is associated with invasive and non-invasive diseases. Methods A total of 395 typeable and 293 NTHi isolates were characterized by whole genome sequencing (WGS). Phylogenetic analysis and multilocus sequence typing were used to characterize the overall genetic diversity. Pair-wise comparisons were used to evaluate the capsule loci. A WGS serotyping method was developed to predict the Hi serotype. WGS serotyping results were compared to slide agglutination (SAST) or real-time PCR (rt-PCR) serotyping. Results Isolates of each Hi serotype clustered into one or two subclades, with each subclade being associated with a distinct sequence type (ST). NTHi isolates were genetically diverse, with seven subclades and 125 STs being detected. Regions I and III of the capsule locus were conserved among the six serotypes (≥82% nucleotide identity). In contrast, genes in Region II were less conserved, with only six gene pairs from all serotypes showing ≥56% nucleotide identity. The WGS serotyping method was 99.9% concordant with SAST and 100% concordant with rt-PCR in determining the Hi serotype. Conclusions Genomic analysis revealed a higher degree of genetic diversity among NTHi compared to typeable Hi. The WGS serotyping method accurately predicted the Hi capsule type and can serve as an alternative method for Hi serotyping.

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“…To understand the emergence of NT-Hi as a cause of invasive disease in the post Hib conjugate vaccine era, comparative genome studies have revealed that NT-Hi showed much higher genetic diversity when compared to Hib or other serotypes that have been regarded as more genetically conserved or clonal [ 104 , 105 ]. Non-encapsulated S. pneumoniaae have also been reported to have higher genetic diversity probably as a result of higher rates of genetic recombination as the capsule may serve as a barrier for foreign DNA uptake [ 21 , 106 ].…”

Section: Molecular Epidemiology Of Invasive Pneumococcal Disease (mentioning

confidence: 99%

“…A platform that uses WGS data for determination of MLST ST and clonal analysis has also been developed [ 133 ]. Use of WGS data to identify genetic typing markers and virulence factors has also been published [ 105 , 118 ]. Pipelines to apply WGS to predict antibiotic susceptibility of bacterial pathogens have been developed [ 134 , 135 ].…”

Section: Whole Genome Sequencing (Wgs) For Molecular Epidemiology mentioning

confidence: 99%

A Narrative Review of the Molecular Epidemiology and Laboratory Surveillance of Vaccine Preventable Bacterial Meningitis Agents: Streptococcus pneumoniae, Neisseria meningitidis, Haemophilus influenzae and Streptococcus agalactiae

Tsang

2021

Microorganisms

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This narrative review describes the public health importance of four most common bacterial meningitis agents, Streptococcus pneumoniae, Neisseria meningitidis, Haemophilus influenzae, and S. agalactiae (group B Streptococcus). Three of them are strict human pathogens that normally colonize the nasopharynx and may invade the blood stream to cause systemic infections and meningitis. S. agalactiae colonizes the genito-gastrointestinal tract and is an important meningitis agent in newborns, but also causes invasive infections in infants or adults. These four bacteria have polysaccharide capsules that protect them against the host complement defense. Currently licensed conjugate vaccines (against S. pneumoniae, H. influenza, and N. meningitidis only but not S. agalactiae) can induce protective serum antibodies in infants as young as two months old offering protection to the most vulnerable groups, and the ability to eliminate carriage of homologous serotype strains in vaccinated subjects lending further protection to those not vaccinated through herd immunity. However, the serotype-specific nature of these vaccines have driven the bacteria to adapt by mechanisms that affect the capsule antigens through either capsule switching or capsule replacement in addition to the possibility of unmasking of strains or serotypes not covered by the vaccines. The post-vaccine molecular epidemiology of vaccine-preventable bacterial meningitis is discussed based on findings obtained with newer genomic laboratory surveillance methods.

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Insights into the population structure and pan-genome of Haemophilus influenzae

Cited by 40 publications

References 81 publications

A heme‐binding protein produced by Haemophilus haemolyticus inhibits non‐typeable Haemophilus influenzae

A heme‐binding protein produced by Haemophilus haemolyticus inhibits non‐typeable Haemophilus influenzae

Genomic characterization of Haemophilus influenzae: a focus on the capsule locus

A Narrative Review of the Molecular Epidemiology and Laboratory Surveillance of Vaccine Preventable Bacterial Meningitis Agents: Streptococcus pneumoniae, Neisseria meningitidis, Haemophilus influenzae and Streptococcus agalactiae

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