Epigenetic cellular memory in Pseudomonas aeruginosa generates phenotypic variation in response to host environments

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 122; no. 27; p. e2415345122
• Main Authors: Vatareck, Elisabeth, Rick, Tim, Oswaldo Gomez, Nicolas, Bandyopadhyay, Arnab, Kramer, Janina, Strunin, Dmytro, Erdmann, Jelena, Hartmann, Oliver, Alpers, Kathrin, Boedeker, Christian, Steffen, Anika, Sieben, Christian, Zhao, Gang, Tomasch, Jürgen, Häussler, Susanne
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences 08.07.2025
• Subjects: Bacterial Proteins - genetics; Bacterial Proteins - metabolism; Disease control; Epigenesis, Genetic; Epigenetic Memory; Epigenetics; Gene expression; Gene Expression Regulation, Bacterial; Gene Regulatory Networks; Heterogeneity; Host-Pathogen Interactions - genetics; Infectious diseases; Natural selection; Opportunist infection; Pathogenicity; Pathogens; Phenotype; Phenotypic variations; Pseudomonas aeruginosa; Pseudomonas aeruginosa - genetics; Pseudomonas aeruginosa - pathogenicity; Pseudomonas Infections - microbiology; GlpD; single-cell; Pseudomonas aeruginosa; glycerol metabolism; epigenetic memory
• ISSN: 0027-8424; 1091-6490; 1091-6490
• DOI: 10.1073/pnas.2415345122

Phenotypic diversification within pathogen populations can enhance survival in stressful environments, broaden niche colonization, and expand the ecological range of infectious diseases due to emerging collective pathogenicity characteristics. We describe a gene regulatory network property in the opportunistic pathogen Pseudomonas aeruginosa that generates diversity of gene expression and pathogenicity behavior at the single-cell level and that is stabilized by epigenetic cellular memory. The resulting heterogeneity in the expression of the glpD gene—an indicator of host-derived glycerol metabolism and intra-host presence—shapes adaptive processes that are subject to natural selection. Our work on how epigenetics generates phenotypic variation in response to the environment and how these changes are inherited to the next generation provides insights into phenotypic diversity and the emergence of unique functionalities at higher levels of organization. These could be crucial for controlling infectious disease outcomes.