Multi-omics profiling reveals atypical sugar utilization and a key membrane composition regulator in Streptococcus pneumoniae
Year: 2025
Type: article
Abstract: The human body comprises many different microenvironments, each with their own challenges for microorganisms to overcome in order to survive and possibly cause infection. The human pathogen Streptococcus pneumoniae is notoriously flexible in this regard, and can adapt to a wide range of host niches, including the nasopharynx, lungs, and cerebrospinal fluid. However, the molecular and genetic foundation of this ability remain largely uncharted. In this work, we demonstrate that niche adaptation imposes genome-wide changes on multiple levels, including gene essentiality, expression and membrane lipid composition, by using infection-mimicking growth conditions. In general, we show that gene expression and fitness profiling couple orthogonal sets of genes to environmental stimuli. For instance, import (manLMN) and catabolism (nagAB) genes are required, but not differentially expressed during growth on N-acetylglucosamine (GlcNAc), opposite to the pattern of other amino sugar metabolism pathways. Surprisingly, we find that pneumococci do not necessarily prefer glucose over GlcNAc and that uptake of GlcNAc in absence of subsequent catabolism is toxic. Moreover, we identify a previously overlooked fatty acid saturation regulator, FasR, controlling membrane composition, rendering it important during heat stress. As nutrient availability and temperature fluctuations are distinctive facets of infection environments, these findings may inform anti-infective strategies.
Source: Nature Communications
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $6,990
Funders: National Science Foundation, U.S. Department of Health and Human Services, Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung, Rijksuniversiteit Groningen, Université de Lausanne, National Institutes of Health, National Institute of Dental and Craniofacial Research, H2020 European Research Council
Awards: G2374388372, G4473052585, G4786419507, Deciphering bacterial transformation: Control and bottlenecks in competence-dependent recombination, scCRISPRi-seq and advanced microscopy to identify key virulence factors and heterogeneous host responses during Streptococcus pneumoniae infection, G6023213073, Uncovering the mechanisms of mycomembrane biogenesis using global CRISPRi screens, The role of cell-to-cell variability in pneumococcal virulence and antibiotic resistance, G8690818240, Investigating Membrane Alterations as a Mechanism of Acid Tolerance in Cariogenic Bacteria
OpenAlex ID: W4416476469