Role of protein aggregates in bacteria

Protein misfolding and aggregation in bacteria, induced by a variety of intrinsic and environmental stresses, have often been associated with proteostasis disruption and toxic effects. However, a growing body of evidence suggests that these aggregates may also serve as functional membrane-less organelles (MLOs), playing a protective role in bacterial cells. The main mechanism responsible for the formation of MLOs is liquid-liquid phase separation (LLPS), a process that transforms a homogenous solution of macromolecules into dense condensates (liquid droplets) and a diluted phase. Over time, these liquid droplets can be transformed into solid aggregates. Bacterial MLOs, containing one dominant component or hundreds of cytoplasmic proteins, have been shown to be involved in various processes, including replication, transcription, cell division, and stress tolerance. The protective function of bacterial MLOs involves sequestration and protection of proteins and RNA from irreversible inactivation or degradation, upregulation of molecular chaperones, and induction of a dormant state. This protective role is particularly significant in the case of pathogenic bacteria exposed to antibiotic therapy. In a dormant state triggered by protein aggregation, pathogens can survive antibiotic therapy as persisters and, after resuming growth, can cause recurrent infections. Recent research has explored the potential use of bacterial MLOs as nanoreactors that catalyze biochemical reactions or serve as protein reservoirs and biosensors, highlighting their potential in biotechnology.