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

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...

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Autores principales: Potts, Caelin C., Topaz, Nadav, Rodriguez-Rivera, Lorraine D., Hu, Fang, Chang, How-Yi, Whaley, Melissa J., Schmink, Susanna, Retchless, Adam C., Chen, Alexander, Ramos, Edward, Doho, Gregory H., Wang, Xin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6790013/
https://www.ncbi.nlm.nih.gov/pubmed/31606037
http://dx.doi.org/10.1186/s12864-019-6145-8
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author Potts, Caelin C.
Topaz, Nadav
Rodriguez-Rivera, Lorraine D.
Hu, Fang
Chang, How-Yi
Whaley, Melissa J.
Schmink, Susanna
Retchless, Adam C.
Chen, Alexander
Ramos, Edward
Doho, Gregory H.
Wang, Xin
author_facet Potts, Caelin C.
Topaz, Nadav
Rodriguez-Rivera, Lorraine D.
Hu, Fang
Chang, How-Yi
Whaley, Melissa J.
Schmink, Susanna
Retchless, Adam C.
Chen, Alexander
Ramos, Edward
Doho, Gregory H.
Wang, Xin
author_sort Potts, Caelin C.
collection PubMed
description 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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spelling pubmed-67900132019-10-18 Genomic characterization of Haemophilus influenzae: a focus on the capsule locus Potts, Caelin C. Topaz, Nadav Rodriguez-Rivera, Lorraine D. Hu, Fang Chang, How-Yi Whaley, Melissa J. Schmink, Susanna Retchless, Adam C. Chen, Alexander Ramos, Edward Doho, Gregory H. Wang, Xin BMC Genomics Research Article 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. BioMed Central 2019-10-12 /pmc/articles/PMC6790013/ /pubmed/31606037 http://dx.doi.org/10.1186/s12864-019-6145-8 Text en © The Author(s). 2019 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
Potts, Caelin C.
Topaz, Nadav
Rodriguez-Rivera, Lorraine D.
Hu, Fang
Chang, How-Yi
Whaley, Melissa J.
Schmink, Susanna
Retchless, Adam C.
Chen, Alexander
Ramos, Edward
Doho, Gregory H.
Wang, Xin
Genomic characterization of Haemophilus influenzae: a focus on the capsule locus
title Genomic characterization of Haemophilus influenzae: a focus on the capsule locus
title_full Genomic characterization of Haemophilus influenzae: a focus on the capsule locus
title_fullStr Genomic characterization of Haemophilus influenzae: a focus on the capsule locus
title_full_unstemmed Genomic characterization of Haemophilus influenzae: a focus on the capsule locus
title_short Genomic characterization of Haemophilus influenzae: a focus on the capsule locus
title_sort genomic characterization of haemophilus influenzae: a focus on the capsule locus
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6790013/
https://www.ncbi.nlm.nih.gov/pubmed/31606037
http://dx.doi.org/10.1186/s12864-019-6145-8
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