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The extensive cellular signalling events controlled by posttranslational ubiquitination are tightly regulated through the action of specialized proteases termed deubiquitinases. Among them, the OTU family of deubiquitinases can play very specialized roles in the regulation of discrete subtypes of ubiquitin signals that control specific cellular functions. To exert control over host cellular functions, some pathogenic bacteria have usurped the OTU deubiquitinase fold as a secreted virulence factor that interferes with ubiquitination inside infected cells. Herein, we provide a review of the function of bacterial OTU deubiquitinases during infection, the structural basis for their deubiquitinase activities and the bioinformatic approaches leading to their identification. Understanding bacterial OTU deubiquitinases holds the potential for discoveries not only in bacterial pathogenesis but in eukaryotic biology as well. [ABSTRACT FROM AUTHOR]

Needle match The needle complex or 'injectisome' that transfers proteins from bacteria to eukaryotic cells is a virulence factor in many bacterial pathogens. A new study of the Salmonella typhimurium injectisome throws light on the mechanism by which 'needles' are produced with the appropriate length. Assembly of multi-component supramolecular machines is fundamental to biology, yet in most cases, assembly pathways and their control are poorly understood. An example is the type III secretion machine, which mediates the transfer of bacterial virulence proteins into host cells.sup.1. A central component of this nanomachine is the needle complex or injectisome, an organelle associated with the bacterial envelope that is composed of a multi-ring base, an inner rod, and a protruding needle.sup.2. Assembly of this organelle proceeds in sequential steps that require the reprogramming of the secretion machine. Here we provide evidence that, in Salmonella typhimurium, completion of the assembly of the inner rod determines the size of the needle substructure. Assembly of the inner rod, which is regulated by the InvJ protein, triggers conformational changes on the cytoplasmic side of the injectisome, reprogramming the secretion apparatus to stop secretion of the needle protein., Author(s): Thomas C. Marlovits [sup.1] [sup.2] [sup.4] [sup.5] , Tomoko Kubori [sup.1] [sup.4] [sup.5] , María Lara-Tejero [sup.1] , Dennis Thomas [sup.3] , Vinzenz M. Unger [sup.2] , Jorge E. [...]

An essential component of type III secretion systems (TTSS) is a supramolecular structure termed the needle complex. In Salmonella enterica, at least four proteins make up this structure: InvG, PrgH, PrgK, and PrgI. Another protein, PrgJ, is thought to play a role in the assembly of this structure, but its function is poorly understood. We have analyzed the expression and localization of PrgJ and the needle protein PrgI in different S. enterica serovar Typhimurium mutant strains. We found that the levels of PrgI and PrgJ were significantly reduced in a TTSS-deficient invA mutant strain and that the decreased levels were due to protein instability. In addition, we found that PrgJ, although associated with the needle complex in wild-type S. enterica serovar Typhimurium, was absent from needle complexes obtained from an invJ mutant strain, which exhibits very long needle substructures. We suggest that PrgJ is involved in capping the needle substructure of the needle complex.

The intracellular bacterial pathogen Legionella pneumophila utilizes the Dot/Icm type IV secretion system to translocate approximately 300 effector proteins to establish a replicative niche known as the Legionella‐containing vacuole. The Dot/Icm system is classified as a type IVB secretion system, which is evolutionarily closely related to the I‐type conjugation systems and is distinct from type IVA secretion systems, such as the Agrobacterium VirB/D4 system. Although both type IVA and IVB systems directly transport nucleic acids or proteins into the cytosol of recipient cells, the components and architecture of type IVB systems are much more complex than those of type IVA systems. Taking full advantage of rapidly developing cryo‐electron microscopy techniques, the structural details of the transport apparatus and coupling complexes in the Dot/Icm system have been clarified in the past few years. In this review, we summarize recent progress in the structural studies of the L. pneumophila type IVB secretion system and the insights gained into the mechanisms of substrate recognition and transport. [ABSTRACT FROM AUTHOR]

Research has been conducted on Salmonella enterica which encodes type II secretion system. Results indicate the importance of Salmonella protein InvE for the bacterial protein translocation into host cells.

A genetic analysis of the pathogenicity island that forms the supramolecular structure, needle complex asembly, in Salmonella enterica serovar Typhimurium type 111 is presented. Results demonstrate that the assembly proceeds in discrete, genetically separable steps, which involve a sec-dependent step and a sec-independent process.

The early stages of flagellar assembly and the cytoplasmic components of the flagella were analyzed in Salmonella typhimurium by utilizing anti-FliG, -FliM and -FliN antibodies. Analysis of flagellar assembly by immunoblotting indicated the role of the FliF MS ring protein in mediating the association between the cell membrane and the switch complex formed by FliG, FliM and FliN. Furthermore, the switch complex assembled on the MS ring complex during the early stages of flagellar assembly.

Research shows that the activities of the bacterial type III protein secretion systems effector protein, important for virulence of bacterial pathogens, are temporally regulated within host cells by virtue of protein's ability to differentially adjust its stability, as exemplified by Salmonella virulence effector.

• Bacterial pathogens have diverse deubiquitinases. • Canonical deubiquitinases in bacteria mostly belong to clan CA or CE proteases. • Legionella has an unprecedented number of ubiquitin ligases and deubiquitinases. • Legionella effector network involves modulation of the host ubiquitin system. Bacterial pathogens utilize eukaryotic cellular systems in various ways for their own benefits. To counteract host immune responses and survive in cells, bacteria modify host signaling pathways. For this aim, they have evolved virulence secretion systems. Bacteria-encoded effector proteins delivered via these secretion systems are the key players in bacterial pathogenesis. Ubiquitination is a post-translational modification that governs eukaryotic cellular systems. Recent studies have revealed that many bacterial effector proteins target the host ubiquitin system, often acting as ubiquitin-modulating enzymes such as ubiquitin ligases and deubiquitinases. Emerging lines of evidence have unveiled the diversity of bacterial deubiquitinases and have provided insights into the bacterial strategy to exploit the host ubiquitin system. [ABSTRACT FROM AUTHOR]

Many bacterial pathogens of plants and animals have evolved a specialized protein-secretion system termed type III to deliver bacterial proteins into host cells. These proteins stimulate or interfere with host cellular functions for the pathogen's benefit. The Salmonella typhimurium pathogenicity island 1 encodes one of these systems that mediates this bacterium's ability to enter nonphagocytic cells. Several components of this type III secretion system are organized in a supramolecular structure termed the needle complex. This structure is made of discrete substructures including a base that spans both membranes and a needle-like projection that extends outward from the bacterial surface. We demonstrate here that the type III secretion export apparatus is required for the assembly of the needle substructure but is dispensable for the assembly of the base. We show that the length of the needle segment is determined by the type III secretion associated protein InvJ. We report that InvG, PrgH, and PrgK constitute the base and that Prgl is the main component of the needle of the type III secretion complex. Prgl homologs are present in type III secretion systems from bacteria pathogenic for animals but are absent from bacteria pathogenic for plants. We hypothesize that the needle component may establish the specificity of type III secretion systems in delivering proteins into either plant or animal cells. bacterial pathogenesis | type III secretion | organelle assembly