Genomic Stability and Genetic Defense Systems in Dolosigranulum pigrum , a Candidate Beneficial Bacterium from the Human Microbiome
| Autor: | Sean L. Cotton, Silvio D. Brugger, Richard J. Roberts, Lindsey Bomar, Isabel F. Escapa, Chelsey A. Skeete, Sara M Eslami, Dakota S Jones, Katherine P. Lemon, Christopher D Johnston, Samuel S. Minot, Stephany Flores Ramos, Wei Gao, Tommy H Tran |
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| Přispěvatelé: | University of Zurich, Johnston, Christopher D, Lemon, Katherine P |
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
pangenome
1303 Biochemistry Physiology nasal microbiota Context (language use) 610 Medicine & health methylome Biology Dolosigranulum pigrum medicine.disease_cause Biochemistry Genome Microbiology 10234 Clinic for Infectious Diseases 1311 Genetics Genetics medicine 1312 Molecular Biology 1706 Computer Science Applications Molecular Biology Ecology Evolution Behavior and Systematics Prophage 2404 Microbiology Human microbiome mobile genetic elements 1314 Physiology QR1-502 restriction modification Computer Science Applications 1105 Ecology Evolution Behavior and Systematics CRISPR Modeling and Simulation Horizontal gene transfer Mobilome Mobile genetic elements Research Article 2611 Modeling and Simulation |
| Zdroj: | mSystems, Vol 6, Iss 5 (2021) mSystems |
| ISSN: | 2379-5077 |
| DOI: | 10.1128/mSystems.00425-21 |
| Popis: | Dolosigranulum pigrum is positively associated with indicators of health in multiple epidemiological studies of human nasal microbiota. Knowledge of the basic biology of D. pigrum is a prerequisite for evaluating its potential for future therapeutic use; however, such data are very limited. To gain insight into D. pigrum’s chromosomal structure, pangenome, and genomic stability, we compared the genomes of 28 D. pigrum strains that were collected across 20 years. Phylogenomic analysis showed closely related strains circulating over this period and closure of 19 genomes revealed highly conserved chromosomal synteny. Gene clusters involved in the mobilome and in defense against mobile genetic elements (MGEs) were enriched in the accessory genome versus the core genome. A systematic analysis for MGEs identified the first candidate D. pigrum prophage and insertion sequence. A systematic analysis for genetic elements that limit the spread of MGEs, including restriction modification (RM), CRISPR-Cas, and deity-named defense systems, revealed strain-level diversity in host defense systems that localized to specific genomic sites, including one RM system hot spot. Analysis of CRISPR spacers pointed to a wealth of MGEs against which D. pigrum defends itself. These results reveal a role for horizontal gene transfer and mobile genetic elements in strain diversification while highlighting that in D. pigrum this occurs within the context of a highly stable chromosomal organization protected by a variety of defense mechanisms. IMPORTANCE Dolosigranulum pigrum is a candidate beneficial bacterium with potential for future therapeutic use. This is based on its positive associations with characteristics of health in multiple studies of human nasal microbiota across the span of human life. For example, high levels of D. pigrum nasal colonization in adults predicts the absence of Staphylococcus aureus nasal colonization. Also, D. pigrum nasal colonization in young children is associated with healthy control groups in studies of middle ear infections. Our analysis of 28 genomes revealed a remarkable stability of D. pigrum strains colonizing people in the United States across a 20-year span. We subsequently identified factors that can influence this stability, including genomic stability, phage predators, the role of MGEs in strain-level variation, and defenses against MGEs. Finally, these D. pigrum strains also lacked predicted virulence factors. Overall, these findings add additional support to the potential for D. pigrum as a therapeutic bacterium. |
| Databáze: | OpenAIRE |
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