Polyphosphate-mediated heavy metal sequestration in non-genetically modified bacteria: mechanisms and...

Human activities are increasing the bioavailability of metals and metalloids, creating serious environmental and health risks. Specifically, there is significant ecotoxicological interest in metalloid (arsenic (As)) and six heavy metals (HMs; cadmium (Cd), chromium (Cr), copper (Cu), lead (Pb), mercury (Hg), and zinc (Zn)) due to their worldwide distribution in all habitats and highly toxic effects on terrestrial and aquatic biota. Understanding toxicity and persistence of HMs is essential for developing effective bioremediation strategies. Bacteria and archaea have evolved diverse cellular adaptations to resist HM toxicity, employing ATP-dependent (active) and ATP-independent (passive) substrate-specific mechanisms. Among them, bioaccumulation via polyphosphate (polyP) inclusions (intracellular) and/or granules (extracellular) has emerged as a central detoxification strategy. Cation-polyP complexes within bacterial structures facilitate metal immobilization, offering a viable approach for reducing HM bioavailability and cellular toxicity. Here, we synthesize the current knowledge on non-genetically modified HM-resistant bacteria, emphasizing bioaccumulation mechanisms mediated by polyP. To date, the role of polyP-mediated bioaccumulation in wild-type bacterial systems remains underexplored and lacks a comprehensive synthesis in the literature. Specifically, we explore (i) the primary bacterial strategies for HM sequestration, (ii) the chronological development of a global understanding of bacterial HM polyP-mediated bioaccumulation, and (iii) emerging biotechnological applications and future perspectives for implementing this strategy in contaminated environments. In contrast to earlier reviews, this work focuses on wild-type, non-genetically modified bacteria and emphasizes the role of polyP-mediated HM bioaccumulation as a resistance mechanism in natural habitats, which can be used for biotechnological applications in resource recovery and HM bioremediation.