Epigenetic Regulation Alters Biofilm Architecture and Composition in Multiple Clinical Isolates of Nontypeable <named-content content-type="genus-species">Haemophilus influenzae</named-content>

ABSTRACT Biofilms play a critical role in the colonization, persistence, and pathogenesis of many human pathogens. Multiple mucosa-associated pathogens have evolved a mechanism of rapid adaptation, termed the phasevarion, which facilitates a coordinated regulation of numerous genes throughout the ba...

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Autores principales:	Kenneth L. Brockman, Patrick N. Azzari, M. Taylor Branstool, John M. Atack, Benjamin L. Schulz, Freda E.-C. Jen, Michael P. Jennings, Lauren O. Bakaletz
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2018
Materias:	DNABII HU NTHI eDNA otitis media phasevarion Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/7b3ecef685634578bbef392691b90abb
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spelling	oai:doaj.org-article:7b3ecef685634578bbef392691b90abb2021-11-15T15:58:20ZEpigenetic Regulation Alters Biofilm Architecture and Composition in Multiple Clinical Isolates of Nontypeable <named-content content-type="genus-species">Haemophilus influenzae</named-content>10.1128/mBio.01682-182150-7511https://doaj.org/article/7b3ecef685634578bbef392691b90abb2018-11-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.01682-18https://doaj.org/toc/2150-7511ABSTRACT Biofilms play a critical role in the colonization, persistence, and pathogenesis of many human pathogens. Multiple mucosa-associated pathogens have evolved a mechanism of rapid adaptation, termed the phasevarion, which facilitates a coordinated regulation of numerous genes throughout the bacterial genome. This epigenetic regulation occurs via phase variation of a DNA methyltransferase, Mod. The phasevarion of nontypeable Haemophilus influenzae (NTHI) significantly affects the severity of experimental otitis media and regulates several disease-related processes. However, the role of the NTHI phasevarion in biofilm formation is unclear. The present study shows that the phasevarions of multiple NTHI clinical isolates regulate in vitro biofilm formation under disease-specific microenvironmental conditions. The impact of phasevarion regulation was greatest under alkaline conditions that mimic those known to occur in the middle ear during disease. Under alkaline conditions, NTHI strains that express the ModA2 methyltransferase formed biofilms with significantly greater biomass and less distinct architecture than those formed by a ModA2-deficient population. The biofilms formed by NTHI strains that express ModA2 also contained less extracellular DNA (eDNA) and significantly less extracellular HU, a DNABII DNA-binding protein critical for biofilm structural stability. Stable biofilm structure is critical for bacterial pathogenesis and persistence in multiple experimental models of disease. These results identify a role for the phasevarion in regulation of biofilm formation, a process integral to the chronic nature of many infections. Understanding the role of the phasevarion in biofilm formation is critical to the development of prevention and treatment strategies for these chronic diseases. IMPORTANCE Upper respiratory tract infections are the number one reason for a child to visit the emergency department, and otitis media (middle ear infection) ranks third overall. Biofilms contribute significantly to the chronic nature of bacterial respiratory tract infections, including otitis media, and make these diseases particularly difficult to treat. Several mucosa-associated human pathogens utilize a mechanism of rapid adaptation termed the phasevarion, or phase variable regulon, to resist environmental and host immune pressures. In this study, we assessed the role of the phasevarion in regulation of biofilm formation by nontypeable Haemophilus influenzae (NTHI), which causes numerous respiratory tract diseases. We found that the NTHI phasevarion regulates biofilm structure and critical biofilm matrix components under disease-specific conditions. The findings of this work could be significant in the design of improved strategies against NTHI infections, as well as diseases due to other pathogens that utilize a phasevarion.Kenneth L. BrockmanPatrick N. AzzariM. Taylor BranstoolJohn M. AtackBenjamin L. SchulzFreda E.-C. JenMichael P. JenningsLauren O. BakaletzAmerican Society for MicrobiologyarticleDNABIIHUNTHIeDNAotitis mediaphasevarionMicrobiologyQR1-502ENmBio, Vol 9, Iss 5 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	DNABII HU NTHI eDNA otitis media phasevarion Microbiology QR1-502
spellingShingle	DNABII HU NTHI eDNA otitis media phasevarion Microbiology QR1-502 Kenneth L. Brockman Patrick N. Azzari M. Taylor Branstool John M. Atack Benjamin L. Schulz Freda E.-C. Jen Michael P. Jennings Lauren O. Bakaletz Epigenetic Regulation Alters Biofilm Architecture and Composition in Multiple Clinical Isolates of Nontypeable <named-content content-type="genus-species">Haemophilus influenzae</named-content>
description	ABSTRACT Biofilms play a critical role in the colonization, persistence, and pathogenesis of many human pathogens. Multiple mucosa-associated pathogens have evolved a mechanism of rapid adaptation, termed the phasevarion, which facilitates a coordinated regulation of numerous genes throughout the bacterial genome. This epigenetic regulation occurs via phase variation of a DNA methyltransferase, Mod. The phasevarion of nontypeable Haemophilus influenzae (NTHI) significantly affects the severity of experimental otitis media and regulates several disease-related processes. However, the role of the NTHI phasevarion in biofilm formation is unclear. The present study shows that the phasevarions of multiple NTHI clinical isolates regulate in vitro biofilm formation under disease-specific microenvironmental conditions. The impact of phasevarion regulation was greatest under alkaline conditions that mimic those known to occur in the middle ear during disease. Under alkaline conditions, NTHI strains that express the ModA2 methyltransferase formed biofilms with significantly greater biomass and less distinct architecture than those formed by a ModA2-deficient population. The biofilms formed by NTHI strains that express ModA2 also contained less extracellular DNA (eDNA) and significantly less extracellular HU, a DNABII DNA-binding protein critical for biofilm structural stability. Stable biofilm structure is critical for bacterial pathogenesis and persistence in multiple experimental models of disease. These results identify a role for the phasevarion in regulation of biofilm formation, a process integral to the chronic nature of many infections. Understanding the role of the phasevarion in biofilm formation is critical to the development of prevention and treatment strategies for these chronic diseases. IMPORTANCE Upper respiratory tract infections are the number one reason for a child to visit the emergency department, and otitis media (middle ear infection) ranks third overall. Biofilms contribute significantly to the chronic nature of bacterial respiratory tract infections, including otitis media, and make these diseases particularly difficult to treat. Several mucosa-associated human pathogens utilize a mechanism of rapid adaptation termed the phasevarion, or phase variable regulon, to resist environmental and host immune pressures. In this study, we assessed the role of the phasevarion in regulation of biofilm formation by nontypeable Haemophilus influenzae (NTHI), which causes numerous respiratory tract diseases. We found that the NTHI phasevarion regulates biofilm structure and critical biofilm matrix components under disease-specific conditions. The findings of this work could be significant in the design of improved strategies against NTHI infections, as well as diseases due to other pathogens that utilize a phasevarion.
format	article
author	Kenneth L. Brockman Patrick N. Azzari M. Taylor Branstool John M. Atack Benjamin L. Schulz Freda E.-C. Jen Michael P. Jennings Lauren O. Bakaletz
author_facet	Kenneth L. Brockman Patrick N. Azzari M. Taylor Branstool John M. Atack Benjamin L. Schulz Freda E.-C. Jen Michael P. Jennings Lauren O. Bakaletz
author_sort	Kenneth L. Brockman
title	Epigenetic Regulation Alters Biofilm Architecture and Composition in Multiple Clinical Isolates of Nontypeable <named-content content-type="genus-species">Haemophilus influenzae</named-content>
title_short	Epigenetic Regulation Alters Biofilm Architecture and Composition in Multiple Clinical Isolates of Nontypeable <named-content content-type="genus-species">Haemophilus influenzae</named-content>
title_full	Epigenetic Regulation Alters Biofilm Architecture and Composition in Multiple Clinical Isolates of Nontypeable <named-content content-type="genus-species">Haemophilus influenzae</named-content>
title_fullStr	Epigenetic Regulation Alters Biofilm Architecture and Composition in Multiple Clinical Isolates of Nontypeable <named-content content-type="genus-species">Haemophilus influenzae</named-content>
title_full_unstemmed	Epigenetic Regulation Alters Biofilm Architecture and Composition in Multiple Clinical Isolates of Nontypeable <named-content content-type="genus-species">Haemophilus influenzae</named-content>
title_sort	epigenetic regulation alters biofilm architecture and composition in multiple clinical isolates of nontypeable <named-content content-type="genus-species">haemophilus influenzae</named-content>
publisher	American Society for Microbiology
publishDate	2018
url	https://doaj.org/article/7b3ecef685634578bbef392691b90abb
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Epigenetic Regulation Alters Biofilm Architecture and Composition in Multiple Clinical Isolates of Nontypeable <named-content content-type="genus-species">Haemophilus influenzae</named-content>

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