Toward a Universal Switch for Microbial Granulation: Photogranule Insights to Advance Granular Wastewater Treatment

Abstract

Microbial granulation─the assembly of self-immobilized, spheroidal aggregates─is a transformative approach for high-density, energy-efficient wastewater treatment. By concentrating biomass and enhancing resilience to influent fluctuations, granular systems significantly reduce infrastructure footprints. Current granular technologies primarily leverage upflow continuous reactors or sequencing-batch reactors, where specific external selection pressures are imposed to drive granulation. However, granulation remains neither spontaneous nor reliably predictable, and its fundamental biological drivers are poorly understood. Recent advances in photogranules challenge selection-pressure models. Photogranules form from activated-sludge inocula in hydrostatic and hydrodynamic batches and even in CSTRs where classical selection conditions are weak or absent. Moreover, the recurring emergence of compact spheroidal granules across diverse natural and laboratory systems suggests shared, intrinsic biological drivers rather than purely engineered causes. In this Perspective, we propose that the bacterial second messenger c-di-GMP functions as a conserved, Goldilocks-like molecular switch that integrates diverse environmental cues into a coordinated granulation program. We synthesize transcriptomic, biochemical, and genetic evidence and advance three hypotheses linking c-di-GMP signaling and community physiology to granulation. If validated, targeted modulation of c-di-GMP─by genetic or chemical means─could enable predictable, resilient granulation across a wider range of systems, including the continuous horizontal-flow basins that dominate wastewater infrastructure.