Delivering the pain: an overview of the type III secretion system with special consideration for aquatic pathogens

Abstract

Gram-negative bacteria are known to subvert eukaryotic cell physiological mechanisms using a wide array of virulence factors, among which the type three-secretion system (T3SS) is often one of the most important. The T3SS constitutes a needle-like apparatus that the bacterium uses to inject a diverse set of effector proteins directly into the cytoplasm of the host cells where they can hamper the host cellular machinery for a variety of purposes. While the structure of the T3SS is somewhat conserved and well described, effector proteins are much more diverse and specific for each pathogen. The T3SS can remodel the cytoskeleton integrity to promote intracellular invasion, as well as silence specific eukaryotic cell signals, notably to hinder or elude the immune response and cause apoptosis. This is also the case in aquatic bacterial pathogens where the T3SS can often play a central role in the establishment of disease, although it remains understudied in several species of important fish pathogens, notably in Yersinia ruckeri. In the present review, we summarise what is known of the T3SS, with a special focus on aquatic pathogens and suggest some possible avenues for research including the potential to target the T3SS for the development of new anti-virulence drugs.

Membrane-localized expression, production and assembly of Vibrio parahaemolyticus T3SS2 provides evidence for transertion

“…Of the core structural components of the T3SS2 injectisome, the needle protein is the one that links the membranes of the bacteria and the host cell by forming a filament through the extracellular space, allowing for insertion of the injection apparatus into the host membrane to facilitate transfer of bacterial effectors into the host cytosol 27 . While most of the T3SS2 structural components have been characterized, the identity of the needle filament protein, in addition to four others, remains obscure due to low sequence similarity with other T3SS needle proteins 19 , 20 .…”

Fish disease and intestinal microbiota: A close and indivisible relationship

“…13,179 The secretion system T3SS is another critical virulence system found in fish pathogens, mainly in Aeromonas such as Edwarsiella, Vibrio, Flavobacterium and Aeromonas. 180,181 The activity of bacterial T3SS effector proteins usually leads to disorders in signalling pathways and reorganization of the cell cytoskeleton, but also, the pathogenicity mechanism associated with host cell apoptosis seems to be produced by the secretion of a cytotoxic enterotoxin. 182 As part of their arsenal of virulence, bacteria can produce exotoxins with specific cytotoxic activities (e.g.…”

“…Then, instead of killing the competitor strains, T6SS increases the intestinal movements that lead to the expulsion of some commensals of the gut microbiota 13,179 . The secretion system T3SS is another critical virulence system found in fish pathogens, mainly in Aeromonas such as Edwarsiella , Vibrio , Flavobacterium and Aeromonas 180,181 . The activity of bacterial T3SS effector proteins usually leads to disorders in signalling pathways and reorganization of the cell cytoskeleton, but also, the pathogenicity mechanism associated with host cell apoptosis seems to be produced by the secretion of a cytotoxic enterotoxin 182 …”

Transertion is used for localized expression and assembly of Vibrio parahaemolyticus T3SS2

“…The T3SS2 injectosome is a multiprotein complex consisting of ∼19 core structural components, all of which are essential for the functionality of this apparatus ( 15, 16 ). Of these components, the needle protein is the one that links the membranes of the bacteria and the host cell by forming a filament through the extracellular space, allowing for insertion of the injection apparatus into the host membrane to facilitate transfer of bacterial effectors into the host cytosol ( 17 ). While most of the T3SS2 structural components have been characterized, the identity of the needle filament protein, in addition to four others, remains obscure due to low sequence similarity with other T3SS needle proteins ( 15, 16 ).…”