The urinary and genital tract microbiota play a crucial role in unfavorable pregnancy outcomes and genomic instability that start in the womb during fetal development, according to new research from the School of Medicine at the University of Maryland’s ( UMSOM ) Institute of Human Virology ( IHV ) and Center of Excellence of the Global Virus Network( GVN ).
A protein from Mycoplasma fermentans, a type of bacterium that frequently colonizes the urogenital tract, was found to be linked to genomic instability in the study, which was written up on July 17 and published in Proceedings of the National Academy of Sciences for the United States of America( PNAS ). Additionally, this bacterial protein decreased mother mouse fertility and increased the number of birth defects in their young pups.
Davide Zella, PhD, an assistant professor of biochemistry and molecular biology at UMSOM’s IHV, and Robert Gallo, MD, The Homer & amp, Martha Gudelsky Distinguished Professor of Medicine, a co-founder and emeritus director of the organization, as well as the scientific leadership board chair and founder, were the principal investigators behind this study.
Our findings shed light on the previously unrecognized role that the human microbiota plays in genetic abnormalities, as well as broaden our understanding of the relationship between the urogenital tract and human reproductive health.
Lead author of the study and Research Associate of Biochemistry and Molecular Biology at UMSOM’s IHV is Francesca Benedetti, PhD.
According to co-lead author Giovannino Silvestri, PhD, a former Research Associate of Medicine at UMSOM’s IHV,” We aim to further explore the mechanisms underlying these findings and their potential implications for preventing and treating chromosomal abnormalities and genetic diseases.”
The human microbiota is known to have an impact on a variety of factors, including immune system control, metabolism, and susceptibility to infectious diseases. Mycoplasmas, one of these bacterial components, has been connected to a number of cancers.
One Mycoplasma protein, DnaK, has been the subject of research. It is a member of the family of proteins that protects other bacterial proteins from harm and aids in their folding when they are newly made, serving as the so-called” chaperone.” While this protein is good for bacteria, it has less of an impact on animal cells. In this regard, the team had previously shown that this DnaK is absorbed by the body’s cells and interferes with important proteins like the tumor suppressor protein p53 that are responsible for maintaining DNA integrity and preventing cancer.
For this most recent study, scientists developed mice that produce the DnaK protein that Mycoplasma fermentans normally produces. These mice developed genomic instability as a result of exposure to DnaK, where entire genome segments were duplicated or deleted, giving rise to mice with varying numbers of copies of particular genes.
The research team discovered that some of these mice between the ages of 3 and 5 had coordination and movement issues. They discovered that the Grid2 gene, which in humans causes the rare genetic disorder known as spinocerebellar ataxia – 18 ( SCAR18 ), which delays the development of skilled movements and intellectual disabilities, has been deleted in these mice.
According to Dr. Zella,” Remarkably, this is the first instance in which a mouse model has successfully recapitulated an actual human genetic disease, demonstrating the model’s potential for further cancer biology research.”
The female mice that produced the DnaK protein were more than a third unable to conceive. Additionally, more than 20 % of pups born to mothers who ate DnaK protein had a birth defect or deformity of some kind.
According to Dr. Gallo,” The occurrences of genomic instability, in the form of increased copy number variations, could explain the decreased fertility and increased instances of abnormally developed fetuses we observed upon DnaK exposure.” These findings expand on our earlier research, which identified DnaK’s disruptive effects on important proteins involved in the proper repair of damaged DNA and also known to be responsible for the emergence of copy number variations. To better understand the potential ramifications of these findings in cancer and cellular transformation is our ongoing commitment.
The work was praised by UMSOM Dean Mark T. Gladwin, MD, Vice President for Medical Affairs at the University of Maryland, Baltimore, and John Z. and Akiko K. Bowers Distinguished Professor. The question of whether DnaK can affect fetal development in humans is seriously raised by the researchers. Investigating whether neutralizing either the bacteria or this protein could maintain fertility and avoid some birth defects would be a crucial next step, he said.