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Staphylococcus aureus can cause outbreaks and becomes multi-drug resistant through gene mutations and acquiring resistance genes. However, why S. aureus easily adapts to hospital environments, promoting resistance and recurrent infections, remains unknown. Here we show that a specific S. aureus lineage evolved from a clone that expresses the accessory gene regulator (Agr) system to subclones that reversibly suppressed Agr and caused an outbreak in the hospital setting. S. aureus with flexible Agr regulation shows increased ability to acquire antibiotic-resistant plasmids, escape host immunity, and colonize mice. Bacteria with flexible Agr regulation shows altered cytosine genomic methylation, including the decreased 5mC methylation in transcriptional regulator genes (pcrA and rpsD), compared to strains with normal Agr expression patterns. In this work, we discover how altered genomic methylation promotes flexible Agr regulation which is associated with persistent pathogen colonization in the hospital environment.
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http://dx.doi.org/10.1038/s41467-024-54033-3 | DOI Listing |
Nat Genet
September 2025
Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London, UK.
Aberrant DNA methylation has been described in nearly all human cancers, yet its interplay with genomic alterations during tumor evolution is poorly understood. To explore this, we performed reduced representation bisulfite sequencing on 217 tumor and matched normal regions from 59 patients with non-small cell lung cancer from the TRACERx study to deconvolve tumor methylation. We developed two metrics for integrative evolutionary analysis with DNA and RNA sequencing data.
View Article and Find Full Text PDFNature
September 2025
Centre for Evolution and Cancer, Institute of Cancer Research, London, UK.
Cancer development and response to treatment are evolutionary processes, but characterizing evolutionary dynamics at a clinically meaningful scale has remained challenging. Here we develop a new methodology called EVOFLUx, based on natural DNA methylation barcodes fluctuating over time, that quantitatively infers evolutionary dynamics using only a bulk tumour methylation profile as input. We apply EVOFLUx to 1,976 well-characterized lymphoid cancer samples spanning a broad spectrum of diseases and show that initial tumour growth rate, malignancy age and epimutation rates vary by orders of magnitude across disease types.
View Article and Find Full Text PDFLife Sci Alliance
November 2025
Graduate School of Science, Technology and Innovation, Kobe University, Kobe, Japan
Mass-based fingerprinting can characterize microorganisms; however, expansion of these methods to predict specific gene functions is lacking. Therefore, mass fingerprinting was developed to functionally profile a yeast knockout library. Matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) fingerprints of 3,238 knockouts were digitized for correlation with gene ontology (GO).
View Article and Find Full Text PDFSci Justice
September 2025
School of Life Sciences, University of KwaZulu-Natal, Private Bag X54001, Westville, Durban 4000, South Africa. Electronic address:
A compound marker integrates two or more genetic markers into a single assay. The application of compound markers enhances the predictive accuracy of genetic testing by leveraging the strengths of different genetic variations while mitigating the limitations of individual markers. Compound markers include SNP-SNPs, SNP-STRs, DIP-SNPs, DIP-STRs, Multi-In/Dels, CpG-SNPs, CpG-STRs/CpG-In/Del, and Methylation-Microhaplotypes.
View Article and Find Full Text PDFBrain Behav Immun
September 2025
Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. Electronic address:
Background: The proteome is a valuable resource for pinpointing therapeutic targets. Therefore, we conducted a proteome-wide Mendelian randomization (MR) study aimed at identifying potential protein markers and therapeutic targets for Anti-N-Methyl-D-Aspartate Receptor Encephalitis (NMDAR-E).
Methods: Protein quantitative trait loci (pQTLs) were obtained from seven published genome-wide association studies (GWASs) focusing on the plasma proteome, resulting in summary-level data for 734 circulating protein markers.