Continuous Microevolution Accelerates Disease Progression during Sequential Episodes of Infection

Summary: Bacteria adapt to dynamic changes in the host during chronic and recurrent infections. Bacterial microevolution is one type of adaptation that imparts a selective advantage. We hypothesize that recurrent episodes of disease promote microevolution through genetic mutations that modulate dise...

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Main Authors:	Alistair Harrison, Rachael L. Hardison, Audra R. Fullen, Rachel M. Wallace, David M. Gordon, Peter White, Ryan N. Jennings, Sheryl S. Justice, Kevin M. Mason
Format:	Article
Language:	English
Published:	Elsevier 2020-03-01
Series:	Cell Reports
Online Access:	http://www.sciencedirect.com/science/article/pii/S221112472030173X

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spelling	doaj-dd89d5fbb9944f4db3c017775d323dc02020-11-25T02:35:13ZengElsevierCell Reports2211-12472020-03-0130929782988.e3Continuous Microevolution Accelerates Disease Progression during Sequential Episodes of InfectionAlistair Harrison0Rachael L. Hardison1Audra R. Fullen2Rachel M. Wallace3David M. Gordon4Peter White5Ryan N. Jennings6Sheryl S. Justice7Kevin M. Mason8Center for Microbial Pathogenesis, The Abigail Wexner Research Institute at Nationwide Children’s Hospital, Columbus, OH 43205, USACenter for Microbial Pathogenesis, The Abigail Wexner Research Institute at Nationwide Children’s Hospital, Columbus, OH 43205, USACenter for Microbial Pathogenesis, The Abigail Wexner Research Institute at Nationwide Children’s Hospital, Columbus, OH 43205, USACenter for Microbial Pathogenesis, The Abigail Wexner Research Institute at Nationwide Children’s Hospital, Columbus, OH 43205, USAThe Steve and Cindy Rasmussen Institute of Genomic Medicine, The Abigail Wexner Research Institute at Nationwide Children’s Hospital, Columbus, OH 43215, USAThe Steve and Cindy Rasmussen Institute of Genomic Medicine, The Abigail Wexner Research Institute at Nationwide Children’s Hospital, Columbus, OH 43215, USACollege of Veterinary Medicine, The Ohio State University, Columbus, OH 43210, USACenter for Microbial Pathogenesis, The Abigail Wexner Research Institute at Nationwide Children’s Hospital, Columbus, OH 43205, USA; Infectious Disease Institute, The Ohio State University, Columbus, OH 43205, USA; Corresponding authorCenter for Microbial Pathogenesis, The Abigail Wexner Research Institute at Nationwide Children’s Hospital, Columbus, OH 43205, USA; Infectious Disease Institute, The Ohio State University, Columbus, OH 43205, USA; Corresponding authorSummary: Bacteria adapt to dynamic changes in the host during chronic and recurrent infections. Bacterial microevolution is one type of adaptation that imparts a selective advantage. We hypothesize that recurrent episodes of disease promote microevolution through genetic mutations that modulate disease severity. We use a pre-clinical model of otitis media (OM) to determine the potential role for microevolution of nontypeable Haemophilus influenzae (NTHI) during sequential episodes of disease. Whole genome sequencing reveals microevolution of hemoglobin binding and lipooligosaccharide (LOS) biosynthesis genes, suggesting that adaptation of these systems is critical for infection. These OM-adapted strains promote increased biofilm formation, inflammation, stromal fibrosis, and an increased propensity to form intracellular bacterial communities (IBCs). Remarkably, IBCs remain for at least one month following clinical resolution of infection, suggesting an intracellular reservoir as a nidus for recurrent OM. Additional approaches for therapeutic design tailored to combat this burdensome disease will arise from these studies. : Harrison et al. develop a sequential model of otitis media (OM) to investigate microevolution through genetic mutations that modulate disease severity. OM-adapted strains promote increased biofilm, inflammation, stromal fibrosis, and intracellular bacterial community (IBC) development. IBCs remain one month following clinical resolution of infection, suggesting a nidus for recurrent OM. Keywords: Haemophilus, microevolution, otitis media, persistence, intracellular bacterial communities, lipooligosaccharide, hemoglobin, recurrencehttp://www.sciencedirect.com/science/article/pii/S221112472030173X
collection	DOAJ
language	English
format	Article
sources	DOAJ
author	Alistair Harrison Rachael L. Hardison Audra R. Fullen Rachel M. Wallace David M. Gordon Peter White Ryan N. Jennings Sheryl S. Justice Kevin M. Mason
spellingShingle	Alistair Harrison Rachael L. Hardison Audra R. Fullen Rachel M. Wallace David M. Gordon Peter White Ryan N. Jennings Sheryl S. Justice Kevin M. Mason Continuous Microevolution Accelerates Disease Progression during Sequential Episodes of Infection Cell Reports
author_facet	Alistair Harrison Rachael L. Hardison Audra R. Fullen Rachel M. Wallace David M. Gordon Peter White Ryan N. Jennings Sheryl S. Justice Kevin M. Mason
author_sort	Alistair Harrison
title	Continuous Microevolution Accelerates Disease Progression during Sequential Episodes of Infection
title_short	Continuous Microevolution Accelerates Disease Progression during Sequential Episodes of Infection
title_full	Continuous Microevolution Accelerates Disease Progression during Sequential Episodes of Infection
title_fullStr	Continuous Microevolution Accelerates Disease Progression during Sequential Episodes of Infection
title_full_unstemmed	Continuous Microevolution Accelerates Disease Progression during Sequential Episodes of Infection
title_sort	continuous microevolution accelerates disease progression during sequential episodes of infection
publisher	Elsevier
series	Cell Reports
issn	2211-1247
publishDate	2020-03-01
description	Summary: Bacteria adapt to dynamic changes in the host during chronic and recurrent infections. Bacterial microevolution is one type of adaptation that imparts a selective advantage. We hypothesize that recurrent episodes of disease promote microevolution through genetic mutations that modulate disease severity. We use a pre-clinical model of otitis media (OM) to determine the potential role for microevolution of nontypeable Haemophilus influenzae (NTHI) during sequential episodes of disease. Whole genome sequencing reveals microevolution of hemoglobin binding and lipooligosaccharide (LOS) biosynthesis genes, suggesting that adaptation of these systems is critical for infection. These OM-adapted strains promote increased biofilm formation, inflammation, stromal fibrosis, and an increased propensity to form intracellular bacterial communities (IBCs). Remarkably, IBCs remain for at least one month following clinical resolution of infection, suggesting an intracellular reservoir as a nidus for recurrent OM. Additional approaches for therapeutic design tailored to combat this burdensome disease will arise from these studies. : Harrison et al. develop a sequential model of otitis media (OM) to investigate microevolution through genetic mutations that modulate disease severity. OM-adapted strains promote increased biofilm, inflammation, stromal fibrosis, and intracellular bacterial community (IBC) development. IBCs remain one month following clinical resolution of infection, suggesting a nidus for recurrent OM. Keywords: Haemophilus, microevolution, otitis media, persistence, intracellular bacterial communities, lipooligosaccharide, hemoglobin, recurrence
url	http://www.sciencedirect.com/science/article/pii/S221112472030173X
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Continuous Microevolution Accelerates Disease Progression during Sequential Episodes of Infection

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