Mycoplasma DnaK increases DNA copy number variants in vivo
The human microbiota affects critical cellular functions, although the responsible mechanism(s) is still poorly understood. In this regard, we previously showed that Mycoplasma fermentans DnaK, an HSP70 chaperone protein, hampers the activity of important cellular proteins responsible for DNA integrity. Here, we describe a novel DnaK knock-in mouse model generated in our laboratory to study the effect of M. fermentans DnaK expression in vivo. By using an array-based comparative genomic hybridization assay, we demonstrate that exposure to DnaK was associated with a higher number of DNA copy number variants (CNVs) indicative of unbalanced chromosomal alterations, together with reduced fertility and a high rate of fetal abnormalities. Consistent with their implication in genetic disorders, one of these CNVs caused a homozygous Grid2 deletion, resulting in an aberrant ataxic phenotype that recapitulates the extensive biallelic deletion in the Grid2 gene classified in humans as autosomal recessive spinocerebellar ataxia 18. Our data highlight a connection between components of the human urogenital tract microbiota, namely Mycoplasmas, and genetic abnormalities in the form of DNA CNVs, with obvious relevant medical, diagnostic, and therapeutic implications.
| Errataetall: |
ErratumIn: Proc Natl Acad Sci U S A. 2023 Dec 19;120(51):e2319798120. - PMID 38079558 |
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| Medienart: |
E-Artikel |
| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:120 |
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| Enthalten in: |
Proceedings of the National Academy of Sciences of the United States of America - 120(2023), 30 vom: 25. Juli, Seite e2219897120 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Benedetti, Francesca [VerfasserIn] |
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| Links: |
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| Themen: |
DNA CNV |
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| Anmerkungen: |
Date Completed 20.11.2023 Date Revised 11.12.2023 published: Print-Electronic ErratumIn: Proc Natl Acad Sci U S A. 2023 Dec 19;120(51):e2319798120. - PMID 38079558 Citation Status MEDLINE |
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| doi: |
10.1073/pnas.2219897120 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 520 | |a The human microbiota affects critical cellular functions, although the responsible mechanism(s) is still poorly understood. In this regard, we previously showed that Mycoplasma fermentans DnaK, an HSP70 chaperone protein, hampers the activity of important cellular proteins responsible for DNA integrity. Here, we describe a novel DnaK knock-in mouse model generated in our laboratory to study the effect of M. fermentans DnaK expression in vivo. By using an array-based comparative genomic hybridization assay, we demonstrate that exposure to DnaK was associated with a higher number of DNA copy number variants (CNVs) indicative of unbalanced chromosomal alterations, together with reduced fertility and a high rate of fetal abnormalities. Consistent with their implication in genetic disorders, one of these CNVs caused a homozygous Grid2 deletion, resulting in an aberrant ataxic phenotype that recapitulates the extensive biallelic deletion in the Grid2 gene classified in humans as autosomal recessive spinocerebellar ataxia 18. Our data highlight a connection between components of the human urogenital tract microbiota, namely Mycoplasmas, and genetic abnormalities in the form of DNA CNVs, with obvious relevant medical, diagnostic, and therapeutic implications | ||
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| 700 | 1 | |a Denaro, Frank |e verfasserin |4 aut | |
| 700 | 1 | |a Latinovic, Olga S |e verfasserin |4 aut | |
| 700 | 1 | |a Davis, Harry |e verfasserin |4 aut | |
| 700 | 1 | |a Williams, Sumiko |e verfasserin |4 aut | |
| 700 | 1 | |a Bryant, Joseph |e verfasserin |4 aut | |
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| 700 | 1 | |a Rathinam, Chozha V |e verfasserin |4 aut | |
| 700 | 1 | |a Gallo, Robert C |e verfasserin |4 aut | |
| 700 | 1 | |a Zella, Davide |e verfasserin |4 aut | |
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