Scientists from the Icahn School of Medicine at Mount Sinai have developed a new technique to more precisely analyze bacterial populations, to reveal epigenetic mechanisms that can drive virulence. The new methods hold the promise of a potent new tool to offset the growing challenge of antibiotic resistance by bacterial pathogens. The research was published today in the journal Nature Communications, and conducted in collaboration with New York University Langone Medical Center and Brigham and Women’s Hospital of Harvard Medical School.
The information content of the genetic code in DNA is not limited to the primary nucleotide sequence of A’s, G’s, C’s and T’s. Individual DNA bases can be chemically modified, with significant functional consequences. In the bacterial kingdom, the most prevalent base modifications are in the form of DNA methylations, specifically to adenine and cytosine residuals. Beyond their participation in host defense, increasing evidence suggests that these modifications also play important roles in the regulation of gene expression, virulence and antibiotic resistance. More.
‘The approach we developed can also be used to analyze DNA viruses and human mitochondrial DNA, both of which present significant epigenetic heterogeneity.’
Really? We were formerly commanded to think that it was all Darwinian evolution.
Here’s the abstract:
Beyond its role in host defense, bacterial DNA methylation also plays important roles in the regulation of gene expression, virulence and antibiotic resistance. Bacterial cells in a clonal population can generate epigenetic heterogeneity to increase population-level phenotypic plasticity. Single molecule, real-time (SMRT) sequencing enables the detection of N6-methyladenine and N4-methylcytosine, two major types of DNA modifications comprising the bacterial methylome. However, existing SMRT sequencing-based methods for studying bacterial methylomes rely on a population-level consensus that lacks the single-cell resolution required to observe epigenetic heterogeneity. Here, we present SMALR (single-molecule modification analysis of long reads), a novel framework for single molecule-level detection and phasing of DNA methylation. Using seven bacterial strains, we show that SMALR yields significantly improved resolution and reveals distinct types of epigenetic heterogeneity. SMALR is a powerful new tool that enables de novo detection of epigenetic heterogeneity and empowers investigation of its functions in bacterial populations. Open access – John Beaulaurier, Xue-Song Zhang, Shijia Zhu, Robert Sebra, Chaggai Rosenbluh, Gintaras Deikus, Nan Shen, Diana Munera, Matthew K. Waldor, Andrew Chess, Martin J. Blaser, Eric E. Schadt, and Gang Fang. “Single molecule-level detection and long read-based phasing of epigenetic variations in bacterial methylomes.” Nature Communications. DOI: 10.1038/ncomms8438
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