Inorganic polyphosphate: a molecule of many functions

Area of Science:

• Biochemistry
• Molecular Biology
• Microbiology

Background:

• Inorganic polyphosphate (poly P) is a ubiquitous polymer of phosphate residues found in all cells.
• Historically, poly P has received limited attention due to a lack of sensitive analytical methods and defined physiological functions.
• Recent advancements in enzymatic assays have enabled deeper investigation into poly P's roles.

Purpose of the Study:

• To review recent advances in understanding inorganic polyphosphate (poly P) functions, driven by novel enzymatic assays.
• To highlight the physiological significance of poly P in cellular stress responses and stationary-phase survival.
• To explore the potential of poly P and its synthesizing enzyme, polyphosphate kinase (PPK), as antimicrobial drug targets.

Main Methods:

• Development and application of novel, sensitive, and high-throughput enzymatic assays using Escherichia coli polyphosphate kinase (PPK) and yeast exopolyphosphatase.
• Genetic manipulation (mutation and overexpression) of PPK genes in E. coli to study poly P synthesis and function.
• Comparative genomic analysis to identify PPK homologs in pathogenic bacteria and subsequent gene knockout studies.
• Identification and isolation of polyphosphatases in yeast and mammalian cells.

Main Results:

• Enzymatic assays using PPK and exopolyphosphatase provide sensitive and facile methods for poly P quantification.
• E. coli studies demonstrate significant poly P accumulation during stress conditions (nutrient deficiency, high salt, nutrient downshift).
• ppk mutants lacking poly P exhibit impaired stationary-phase adaptation, reduced RpoS expression, and rapid cell death, underscoring poly P's critical role in survival.
• Homology of PPK in major pathogens suggests poly P and PPK as potential antimicrobial targets.

Conclusions:

• Novel enzymatic assays have revolutionized the study of inorganic polyphosphate (poly P), revealing its critical importance in cellular stress responses and survival.
• Poly P plays a vital role in bacterial stationary-phase adaptation and survival, with PPK emerging as a promising target for novel antimicrobial therapies.
• Further research into poly P's functions in yeast, mammalian cells, and its potential roles in human development, aging, and disease is warranted, given its ancient origins and broad biological presence.