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Novel Moraxella catarrhalis prophages display hyperconserved non-structural genes despite their genomic diversity

BACKGROUND: Moraxella catarrhalis is an important pathogen that often causes otitis media in children, a disease that is not currently vaccine preventable. Asymptomatic colonisation of the human upper respiratory tract is common and lack of clearance by the immune system is likely due to the emergen...

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Autores principales: Ariff, Amir, Wise, Michael J., Kahler, Charlene M., Tay, Chin Yen, Peters, Fanny, Perkins, Timothy T., Chang, Barbara J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4619438/
https://www.ncbi.nlm.nih.gov/pubmed/26497500
http://dx.doi.org/10.1186/s12864-015-2104-1
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author Ariff, Amir
Wise, Michael J.
Kahler, Charlene M.
Tay, Chin Yen
Peters, Fanny
Perkins, Timothy T.
Chang, Barbara J.
author_facet Ariff, Amir
Wise, Michael J.
Kahler, Charlene M.
Tay, Chin Yen
Peters, Fanny
Perkins, Timothy T.
Chang, Barbara J.
author_sort Ariff, Amir
collection PubMed
description BACKGROUND: Moraxella catarrhalis is an important pathogen that often causes otitis media in children, a disease that is not currently vaccine preventable. Asymptomatic colonisation of the human upper respiratory tract is common and lack of clearance by the immune system is likely due to the emergence of seroresistant genetic lineages. No active bacteriophages or prophages have been described in this species. This study was undertaken to identify and categorise prophages in M. catarrhalis, their genetic diversity and the relationship of such diversity with the host-species phylogeny. RESULTS: This study presents a comparative analysis of 32 putative prophages identified in 95 phylogenetically variable, newly sequenced M. catarrhalis genomes. The prophages were genotypically classified into four diverse clades. The genetic synteny of each clade is similar to the group 1 phage family Siphoviridae, however, they form genotypic clusters that are distinct from other members of this family. No core genetic sequences exist across the 32 prophages despite clades 2, 3, and 4 sharing the most sequence identity. The analysis of non-structural prophage genes (coding the integrase, and terminase), and portal gene showed that the respective genes were identical for clades 2, 3, and 4, but unique for clade 1. Empirical analysis calculated that these genes are unexpectedly hyperconserved, under purifying selection, suggesting a tightly regulated functional role. As such, it is improbable that the prophages are decaying remnants but stable components of a fluctuating, flexible and unpredictable system ultimately maintained by functional constraints on non-structural and packaging genes. Additionally, the plate encoding genes were well conserved across all four prophage clades, and the tail fibre genes, commonly responsible for receptor recognition, were clustered into three major groups distributed across the prophage clades. A pan-genome of 283,622 bp was identified, and the prophages were mapped onto the diverse M. catarrhalis multi-locus sequence type (MLST) backbone. CONCLUSION: This study has provided the first evidence of putatively mobile prophages in M. catarrhalis, identifying a diverse and fluctuating system dependent on the hyperconservation of a few key, non-structural genes. Some prophages harbour virulence-related genes, and potentially influence the physiology and virulence of M. catarrhalis. Importantly our data will provide supporting information on the identification of novel prophages in other species by adding greater weight to the identification of non-structural genes. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12864-015-2104-1) contains supplementary material, which is available to authorized users.
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spelling pubmed-46194382015-10-26 Novel Moraxella catarrhalis prophages display hyperconserved non-structural genes despite their genomic diversity Ariff, Amir Wise, Michael J. Kahler, Charlene M. Tay, Chin Yen Peters, Fanny Perkins, Timothy T. Chang, Barbara J. BMC Genomics Research Article BACKGROUND: Moraxella catarrhalis is an important pathogen that often causes otitis media in children, a disease that is not currently vaccine preventable. Asymptomatic colonisation of the human upper respiratory tract is common and lack of clearance by the immune system is likely due to the emergence of seroresistant genetic lineages. No active bacteriophages or prophages have been described in this species. This study was undertaken to identify and categorise prophages in M. catarrhalis, their genetic diversity and the relationship of such diversity with the host-species phylogeny. RESULTS: This study presents a comparative analysis of 32 putative prophages identified in 95 phylogenetically variable, newly sequenced M. catarrhalis genomes. The prophages were genotypically classified into four diverse clades. The genetic synteny of each clade is similar to the group 1 phage family Siphoviridae, however, they form genotypic clusters that are distinct from other members of this family. No core genetic sequences exist across the 32 prophages despite clades 2, 3, and 4 sharing the most sequence identity. The analysis of non-structural prophage genes (coding the integrase, and terminase), and portal gene showed that the respective genes were identical for clades 2, 3, and 4, but unique for clade 1. Empirical analysis calculated that these genes are unexpectedly hyperconserved, under purifying selection, suggesting a tightly regulated functional role. As such, it is improbable that the prophages are decaying remnants but stable components of a fluctuating, flexible and unpredictable system ultimately maintained by functional constraints on non-structural and packaging genes. Additionally, the plate encoding genes were well conserved across all four prophage clades, and the tail fibre genes, commonly responsible for receptor recognition, were clustered into three major groups distributed across the prophage clades. A pan-genome of 283,622 bp was identified, and the prophages were mapped onto the diverse M. catarrhalis multi-locus sequence type (MLST) backbone. CONCLUSION: This study has provided the first evidence of putatively mobile prophages in M. catarrhalis, identifying a diverse and fluctuating system dependent on the hyperconservation of a few key, non-structural genes. Some prophages harbour virulence-related genes, and potentially influence the physiology and virulence of M. catarrhalis. Importantly our data will provide supporting information on the identification of novel prophages in other species by adding greater weight to the identification of non-structural genes. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12864-015-2104-1) contains supplementary material, which is available to authorized users. BioMed Central 2015-10-24 /pmc/articles/PMC4619438/ /pubmed/26497500 http://dx.doi.org/10.1186/s12864-015-2104-1 Text en © Ariff et al. 2015 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
Ariff, Amir
Wise, Michael J.
Kahler, Charlene M.
Tay, Chin Yen
Peters, Fanny
Perkins, Timothy T.
Chang, Barbara J.
Novel Moraxella catarrhalis prophages display hyperconserved non-structural genes despite their genomic diversity
title Novel Moraxella catarrhalis prophages display hyperconserved non-structural genes despite their genomic diversity
title_full Novel Moraxella catarrhalis prophages display hyperconserved non-structural genes despite their genomic diversity
title_fullStr Novel Moraxella catarrhalis prophages display hyperconserved non-structural genes despite their genomic diversity
title_full_unstemmed Novel Moraxella catarrhalis prophages display hyperconserved non-structural genes despite their genomic diversity
title_short Novel Moraxella catarrhalis prophages display hyperconserved non-structural genes despite their genomic diversity
title_sort novel moraxella catarrhalis prophages display hyperconserved non-structural genes despite their genomic diversity
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4619438/
https://www.ncbi.nlm.nih.gov/pubmed/26497500
http://dx.doi.org/10.1186/s12864-015-2104-1
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