Protein aggregation in bacteria: the thin boundary between functionality and toxicity

• Published in: Microbiology (Society for General Microbiology) 2013-09, Vol.159 (Pt 9), p.1795-1806
• Main Authors: Bednarska, Natalia G, Schymkowitz, Joost, Rousseau, Frederic, Van Eldere, Johan
• Format: Article
• Language: English
• Subjects: Animals; Bacteria - chemistry; Bacteria - genetics; Bacteria - metabolism; Bacteria - pathogenicity; Bacterial Infections - microbiology; Bacterial Proteins - chemistry; Bacterial Proteins - genetics; Bacterial Proteins - metabolism; Humans; Protein Folding; Virulence
• ISSN: 1350-0872; 1465-2080
• DOI: 10.1099/mic.0.069575-0

Misfolding and aggregation of proteins have a negative impact on all living organisms. In recent years, aggregation has been studied in detail due to its involvement in neurodegenerative diseases, including Alzheimer's, Parkinson's and Huntington's diseases, and type II diabetes--all associated with accumulation of amyloid fibrils. This research highlighted the central importance of protein homeostasis, or proteostasis for short, defined as the cellular state in which the proteome is both stable and functional. It implicates an equilibrium between synthesis, folding, trafficking, aggregation, disaggregation and degradation. In accordance with the eukaryotic systems, it has been documented that protein aggregation also reduces fitness of bacterial cells, but although our understanding of the cellular protein quality control systems is perhaps most detailed in bacteria, the use of bacterial proteostasis as a drug target remains little explored. Here we describe protein aggregation as a normal physiological process and its role in bacterial virulence and we shed light on how bacteria defend themselves against the toxic threat of aggregates. We review the impact of aggregates on bacterial viability and look at the ways that bacteria use to maintain a balance between aggregation and functionality. The proteostasis in bacteria can be interrupted via overexpression of proteins, certain antibiotics such as aminoglycosides, as well as antimicrobial peptides--all leading to loss of cell viability. Therefore intracellular protein aggregation and disruption of proteostatic balance in bacteria open up another strategy that should be explored towards the discovery of new antimicrobials.