Cargando…
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 integr...
Autores principales: | , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
National Academy of Sciences
2023
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10372619/ https://www.ncbi.nlm.nih.gov/pubmed/37459550 http://dx.doi.org/10.1073/pnas.2219897120 |
_version_ | 1785078408170962944 |
---|---|
author | Benedetti, Francesca Silvestri, Giovannino Saadat, Saman Denaro, Frank Latinovic, Olga S. Davis, Harry Williams, Sumiko Bryant, Joseph Ippodrino, Rudy Rathinam, Chozha V. Gallo, Robert C. Zella, Davide |
author_facet | Benedetti, Francesca Silvestri, Giovannino Saadat, Saman Denaro, Frank Latinovic, Olga S. Davis, Harry Williams, Sumiko Bryant, Joseph Ippodrino, Rudy Rathinam, Chozha V. Gallo, Robert C. Zella, Davide |
author_sort | Benedetti, Francesca |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-10372619 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | National Academy of Sciences |
record_format | MEDLINE/PubMed |
spelling | pubmed-103726192023-07-28 Mycoplasma DnaK increases DNA copy number variants in vivo Benedetti, Francesca Silvestri, Giovannino Saadat, Saman Denaro, Frank Latinovic, Olga S. Davis, Harry Williams, Sumiko Bryant, Joseph Ippodrino, Rudy Rathinam, Chozha V. Gallo, Robert C. Zella, Davide Proc Natl Acad Sci U S A Biological Sciences 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. National Academy of Sciences 2023-07-17 2023-07-25 /pmc/articles/PMC10372619/ /pubmed/37459550 http://dx.doi.org/10.1073/pnas.2219897120 Text en Copyright © 2023 the Author(s). Published by PNAS. https://creativecommons.org/licenses/by-nc-nd/4.0/This open access article is distributed under Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND) (https://creativecommons.org/licenses/by-nc-nd/4.0/) . |
spellingShingle | Biological Sciences Benedetti, Francesca Silvestri, Giovannino Saadat, Saman Denaro, Frank Latinovic, Olga S. Davis, Harry Williams, Sumiko Bryant, Joseph Ippodrino, Rudy Rathinam, Chozha V. Gallo, Robert C. Zella, Davide Mycoplasma DnaK increases DNA copy number variants in vivo |
title | Mycoplasma DnaK increases DNA copy number variants in vivo |
title_full | Mycoplasma DnaK increases DNA copy number variants in vivo |
title_fullStr | Mycoplasma DnaK increases DNA copy number variants in vivo |
title_full_unstemmed | Mycoplasma DnaK increases DNA copy number variants in vivo |
title_short | Mycoplasma DnaK increases DNA copy number variants in vivo |
title_sort | mycoplasma dnak increases dna copy number variants in vivo |
topic | Biological Sciences |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10372619/ https://www.ncbi.nlm.nih.gov/pubmed/37459550 http://dx.doi.org/10.1073/pnas.2219897120 |
work_keys_str_mv | AT benedettifrancesca mycoplasmadnakincreasesdnacopynumbervariantsinvivo AT silvestrigiovannino mycoplasmadnakincreasesdnacopynumbervariantsinvivo AT saadatsaman mycoplasmadnakincreasesdnacopynumbervariantsinvivo AT denarofrank mycoplasmadnakincreasesdnacopynumbervariantsinvivo AT latinovicolgas mycoplasmadnakincreasesdnacopynumbervariantsinvivo AT davisharry mycoplasmadnakincreasesdnacopynumbervariantsinvivo AT williamssumiko mycoplasmadnakincreasesdnacopynumbervariantsinvivo AT bryantjoseph mycoplasmadnakincreasesdnacopynumbervariantsinvivo AT ippodrinorudy mycoplasmadnakincreasesdnacopynumbervariantsinvivo AT rathinamchozhav mycoplasmadnakincreasesdnacopynumbervariantsinvivo AT gallorobertc mycoplasmadnakincreasesdnacopynumbervariantsinvivo AT zelladavide mycoplasmadnakincreasesdnacopynumbervariantsinvivo |