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dc.contributor.authorBrockman, Kenneth L
dc.contributor.authorAzzari, Patrick N
dc.contributor.authorBranstool, M Taylor
dc.contributor.authorAtack, John M
dc.contributor.authorSchulz, Benjamin L
dc.contributor.authorJen, Freda E-C
dc.contributor.authorJennings, Michael P
dc.contributor.authorBakaletz, Lauren O
dc.date.accessioned2019-06-09T01:32:52Z
dc.date.available2019-06-09T01:32:52Z
dc.date.issued2018
dc.identifier.issn2150-7511
dc.identifier.doi10.1128/mBio.01682-18
dc.identifier.urihttp://hdl.handle.net/10072/383433
dc.description.abstractBiofilms 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.
dc.description.peerreviewedYes
dc.languageEnglish
dc.publisherAMER SOC MICROBIOLOGY
dc.relation.ispartofissue5
dc.relation.ispartofjournalMBIO
dc.relation.ispartofvolume9
dc.subject.fieldofresearchMicrobiology
dc.subject.fieldofresearchcode0605
dc.titleEpigenetic Regulation Alters Biofilm Architecture and Composition in Multiple Clinical Isolates of Nontypeable Haemophilus influenzae
dc.typeJournal article
dc.type.descriptionC1 - Articles
dc.type.codeC - Journal Articles
dc.description.versionPublished
gro.rights.copyright© 2018 Brockman et al. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license.
gro.hasfulltextFull Text
gro.griffith.authorAtack, John M.
gro.griffith.authorJennings, Michael P.
gro.griffith.authorJen, Freda E.


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