In vivo evolution of an emerging zoonotic bacterial pathogen in an immunocompromised human host
| Autor: | John P. Dekker, Jung-Ho Youn, A. Dulanto Chiang, A. Launay, Pavel P. Khil, Chuan Wu |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Bacterial Zoonoses
DNA repair Bordetella Science General Physics and Astronomy Bordetella hinzii General Biochemistry Genetics and Molecular Biology Poultry Article Evolutionary genetics Bacterial genetics Evolution Molecular 03 medical and health sciences Immunocompromised Host Bacterial Proteins Animals Humans Pathogen Phylogeny 030304 developmental biology DNA Polymerase III Genetics Whole genome sequencing 0303 health sciences Multidisciplinary biology Zoonotic Infection Human evolutionary genetics 030302 biochemistry & molecular biology Receptors Interleukin-12 General Chemistry biology.organism_classification Phenotype Adaptation Physiological Computational biology and bioinformatics Host-Pathogen Interactions Mutation Infection |
| Zdroj: | Nature Communications Nature Communications, Vol 12, Iss 1, Pp 1-12 (2021) |
| ISSN: | 2041-1723 |
| Popis: | Zoonotic transfer of animal pathogens to human hosts can generate novel agents, but the genetic events following such host jumps are not well studied. Here we characterize the mechanisms driving adaptive evolution of the emerging zoonotic pathogen Bordetella hinzii in a patient with interleukin-12 receptor β1 deficiency. Genomic sequencing of 24 B. hinzii isolates cultured from blood and stool over 45 months revealed a clonal lineage that had undergone extensive within-host genetic and phenotypic diversification. Twenty of 24 isolates shared an E9G substitution in the DNA polymerase III ε-subunit active site, resulting in a proofreading deficiency. Within this proofreading-deficient clade, multiple lineages with mutations in DNA repair genes and altered mutational spectra emerged and dominated clinical cultures for more than 12 months. Multiple enzymes of the tricarboxylic acid cycle and gluconeogenesis pathways were repeatedly mutated, suggesting rapid metabolic adaptation to the human environment. Furthermore, an excess of G:C > T:A transversions suggested that oxidative stress shaped genetic diversification during adaptation. We propose that inactivation of DNA proofreading activity in combination with prolonged, but sub-lethal, oxidative attack resulting from the underlying host immunodeficiency facilitated rapid genomic adaptation. These findings suggest a fundamental role for host immune phenotype in shaping pathogen evolution following zoonotic infection. Bordetella hinzii is an emerging pathogen with zoonotic risk to humans, known to be able to cause respiratory tract infection, bacteremia and endocarditis. Here, applying whole genome sequencing to bacterial isolates, the authors characterize the mechanisms driving adaptive evolution in B. hinzii in a patient with interleukin-12 receptor β1 deficiency, suggesting a role for host immune phenotype in shaping within-host pathogen evolution following zoonotic infection. |
| Databáze: | OpenAIRE |
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