ClpB, a member of class 1 AAA+ proteins, is a key chaperone with disaggregase activity. It plays a crucial role in bacterial survival under various stress conditions, such as heat shock, and is also involved in regulating the secretion of bacterial effector molecules related to type VI secretion systems [1]. In plants, it is essential for heat stress tolerance, and in bacteria, it cooperates with the DnaK chaperone system to reactivate aggregated proteins and promote survival under adverse conditions [3,4,5]. Since ClpB is not present in human cells, it is an attractive target for antimicrobial therapies [3].

CLPB mutations are associated with 3-methylglutaconic aciduria and neutropenia. In a CLPB-null environment, there is a stress-specific aggregation phenotype, and CLPB deficiency impedes the function of the proteolytic SPY complex due to protein aggregation in the mitochondrial intermembrane space, indicating an interdependency of mitochondrial quality control components at the intermembrane space/inner membrane interface [2].

In conclusion, ClpB is vital for stress responses in bacteria and plants, with its disaggregase activity being key to protein reactivation and survival under stress. In humans, mutations in CLPB are associated with neutropenia and mitochondrial-related diseases. Studies on ClpB provide insights into bacterial virulence, plant stress tolerance, and human mitochondrial chaperonopathies, potentially guiding the development of novel antimicrobial therapies and understanding of related disease mechanisms.