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PreprintCC BY-NDbioRxiv

Reducing growth-medium complexity reveals nutrient-responsive programs in a near-minimal bacterium

  1. 1Usherbrooke

Abstract

Mesoplasma florum is a fast-growing, near-minimal bacterium and an emerging model for systems and synthetic biology. However, its dependence on complex serum-containing media limits experimental control and complicates the interpretation of cellular phenotypes. Here, we developed CMRL-AT, a serum-free, quasi-defined medium that supports rapid growth comparable to the commonly used ATCC 1161 medium. Despite supporting similar biomass, CMRL-AT profoundly reshaped the M. florum transcriptome, with approximately one-third of the annotated protein-encoding genes being differentially expressed relative to ATCC 1161. These changes revealed distinct physiological programs associated with rapid growth in complex medium and higher nutrient acquisition in CMRL-AT, illustrating how medium composition alters the functional priorities of a near-minimal cell. Transcriptome profiling across six energy sources further uncovered distinct sugar-responsive expression programs. Combining these responses with transcription-unit organization, protein-domain predictions, and metabolic context resolved fructose- and sucrose-responsive modules, and allowed the assignment of previously ambiguous phosphotransferase system components to specific sugar-utilization pathways. CMRL-AT provides an experimental framework to help resolving gene functions, refining metabolic models, and designing reduced genomes adapted to defined environments.

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BibTeX
@misc{duval2026reducing,
  title = {{Reducing growth-medium complexity reveals nutrient-responsive programs in a near-minimal bacterium}},
  author = {A. Duval and J. Gagnon and S. Jeanneau and D. Matteau and P.-E. Jacques and S. Rodrigue},
  howpublished = {bioRxiv},
  year = {2026},
  month = sep,
  doi = {10.64898/2026.09.29.755377},
  url = {https://www.biorxiv.org/content/10.64898/2026.09.29.755377v1},
  note = {CC BY-ND},
}
RIS
TY  - UNPB
TI  - Reducing growth-medium complexity reveals nutrient-responsive programs in a near-minimal bacterium
AU  - A. Duval
AU  - J. Gagnon
AU  - S. Jeanneau
AU  - D. Matteau
AU  - P.-E. Jacques
AU  - S. Rodrigue
PY  - 2026
DA  - 2026/09/29
PB  - bioRxiv
DO  - 10.64898/2026.09.29.755377
UR  - https://www.biorxiv.org/content/10.64898/2026.09.29.755377v1
AB  - Mesoplasma florum is a fast-growing, near-minimal bacterium and an emerging model for systems and synthetic biology. However, its dependence on complex serum-containing media limits experimental control and complicates the interpretation of cellular phenotypes. Here, we developed CMRL-AT, a serum-free, quasi-defined medium that supports rapid growth comparable to the commonly used ATCC 1161 medium. Despite supporting similar biomass, CMRL-AT profoundly reshaped the M. florum transcriptome, with approximately one-third of the annotated protein-encoding genes being differentially expressed relative to ATCC 1161. These changes revealed distinct physiological programs associated with rapid growth in complex medium and higher nutrient acquisition in CMRL-AT, illustrating how medium composition alters the functional priorities of a near-minimal cell. Transcriptome profiling across six energy sources further uncovered distinct sugar-responsive expression programs. Combining these responses with transcription-unit organization, protein-domain predictions, and metabolic context resolved fructose- and sucrose-responsive modules, and allowed the assignment of previously ambiguous phosphotransferase system components to specific sugar-utilization pathways. CMRL-AT provides an experimental framework to help resolving gene functions, refining metabolic models, and designing reduced genomes adapted to defined environments.
ER  -