Epigenetic Regulation Alters Biofilm Architecture and Composition in Multiple Clinical Isolates of Nontypeable Haemophilus influenzae

MBio
Kenneth L BrockmanLauren O Bakaletz

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 ex...Continue Reading

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Citations

Jan 26, 2020·FEMS Microbiology Reviews·Dan I AnderssonTone Tønjum
Nov 17, 2020·Frontiers in Cellular and Infection Microbiology·Frank H Robledo-AvilaKenneth L Brockman
Jan 19, 2021·Critical Reviews in Microbiology·Bryn ShortS Lorraine Martin
Dec 28, 2019·International Journal of Pediatric Otorhinolaryngology·R B ThorntonK L Brockman
Jun 18, 2021·Computational and Structural Biotechnology Journal·Nahikari López-LópezJunkal Garmendia
Aug 10, 2021·Frontiers in Microbiology·Rabeb DhouibUlrike Kappler
Aug 24, 2021·Frontiers in Cellular and Infection Microbiology·Jake R WeeksTom M A Wilkinson

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Methods Mentioned

BETA
reverse transcription-PCR
confocal microscopy
scraping

Software Mentioned

COMSTAT2
GraphPad Prism
EdgeR
COMSTAT
Bioconductor package
GraphPad

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