Polyphosphate synthesis is essential for phosphate and ATP homeostasis during nutrient upshift

• 成果类型: Article
• 署名作者: White, Maria L.; Mortier, Julien; Granqvist, Lova; Omnus, Deike J.; Louski, Max; Crang, Nick; Aldikacti, Berent; Migeot, Valerie; Chien, Peter; Hennequart, Marc; Hallez, Regis; Jonas, Kristina
• 署名单位: Stockholm University; Royal Institute of Technology; University of Massachusetts System; University of Massachusetts Amherst; University of Namur; University of Namur; University of Namur; Flanders Institute for Biotechnology (VIB); Royal Institute of Technology
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.2531128123
• 发表日期: 2026-06-09
• 页码: e2531128123
• 关键词: PolyP; Ppk1; Pst system; nutrient adaptation; Caulobacter crescentus; inorganic polyphosphate; CAULOBACTER-CRESCENTUS; STARVATION RESPONSE; survival; motility; GROWTH

摘要

Inorganic polyphosphate (polyP) is a ubiquitous molecule found across all domains of life. Although implicated in diverse cellular processes, including phosphate storage, stress responses, and pathogenicity, loss of polyP synthesis typically causes only mild growth defects. Here, we demonstrate an essential physiological role for polyP synthesis during recovery from phosphate starvation, when cells transition from phosphate-limited to phosphate-replete conditions. Using a comprehensive transposon sequencing approach in Caulobacter crescentus, we identify genes conferring a fitness advantage during starvation for carbon, nitrogen, or phosphate and during subsequent recovery. We find that ppk1, encoding the polyphosphate kinase responsible for polyP synthesis, is specifically required for recovery from phosphate starvation but dispensable for entry into starvation, a result confirmed with a ppk1 deletion mutant. Mutations that reduce phosphate uptake via the phosphate-specific transport system suppress the requirement for ppk1, indicating that polyP synthesis prevents toxic accumulation of intracellular inorganic phosphate (Pi) upon refeeding. Our findings further show that buffering intracellular Pi through polyP synthesis is critical for maintaining ATP homeostasis. Together, these results define a central role for polyP synthesis in regulating intracellular phosphate balance and ATP homeostasis, thereby facilitating adaptation to fluctuating nutrient conditions.