Bacterial DUBs: deubiquitination beyond the seven classes

Area of Science:

• Cellular Biology
• Microbiology
• Immunology

Background:

• Protein ubiquitination is a crucial posttranslational modification regulating cellular processes and immunity.
• Ubiquitination targets intracellular bacteria for lysosomal degradation, forming a key part of cell-autonomous immunity.
• Pathogenic bacteria often encode deubiquitinases (DUBs) to counteract this immune response.

Purpose of the Study:

• To systematically review known bacterial deubiquitinases (DUBs).
• To analyze their cleavage specificities and biological functions.
• To investigate the evolutionary origins of bacterial DUBs.

Main Methods:

• Systematic literature review of bacterial deubiquitinases.
• Analysis of reported cleavage specificities.
• Examination of biological roles in bacterial pathogenesis and host interaction.

Main Results:

• Identified numerous bacterial DUBs used as secreted effectors.
• Demonstrated that bacterial DUBs prevent the ubiquitination of bacterial components.
• Evidence suggests multiple independent acquisition events of DUBs from hosts.
• Bacterial DUBs often do not fit the established eukaryotic DUB classification.

Conclusions:

• Bacterial DUBs are critical virulence factors that subvert host cell-autonomous immunity.
• The evolutionary origins of bacterial DUBs are diverse, involving horizontal gene transfer.
• Existing eukaryotic DUB classification systems are insufficient for bacterial DUBs.