Continuous Microevolution Accelerates Disease Progression during Sequential Episodes of Infection
| Autor: | Peter White, Rachael L. Hardison, Rachel M. Wallace, Audra R. Fullen, Sheryl S. Justice, Ryan N. Jennings, Kevin M. Mason, David M Gordon, Alistair Harrison |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Lipopolysaccharides
0301 basic medicine Hemoglobin binding Inflammation Disease Biology Infections medicine.disease_cause Polymorphism Single Nucleotide Article General Biochemistry Genetics and Molecular Biology Haemophilus influenzae Hemoglobins 03 medical and health sciences 0302 clinical medicine Bacterial Proteins Chinchilla medicine Animals Gene lcsh:QH301-705.5 Haptoglobins Biofilm Glycosyltransferases Microevolution Adaptation Physiological Fibrosis Biosynthetic Pathways Otitis Media 030104 developmental biology Otitis lcsh:Biology (General) Biofilms Acute Disease Immunology Disease Progression Stromal Cells medicine.symptom 030217 neurology & neurosurgery |
| Zdroj: | Cell Reports, Vol 30, Iss 9, Pp 2978-2988.e3 (2020) Cell reports |
| ISSN: | 2211-1247 |
| Popis: | 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. Graphical Abstract In Brief 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. |
| Databáze: | OpenAIRE |
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