The T3SS of Shigella: Expression, Structure, Function, and Role in Vacuole Escape

Abstract

Shigella spp. are one of the leading causes of infectious diarrheal diseases. They are Escherichia coli pathovars that are characterized by the harboring of a large plasmid that encodes most virulence genes, including a type III secretion system (T3SS). The archetypal element of the T3SS is the injectisome, a syringe-like nanomachine composed of approximately 20 proteins, spanning both bacterial membranes and the cell wall, and topped with a needle. Upon contact of the tip of the needle with the plasma membrane, the injectisome secretes its protein substrates into host cells. Some of these substrates act as translocators or effectors whose functions are key to the invasion of the cytosol and the cell-to-cell spread characterizing the lifestyle of Shigella spp. Here, we review the structure, assembly, function, and methods to measure the activity of the injectisome with a focus on Shigella, but complemented with data from other T3SS if required. We also present the regulatory cascade that controls the expression of T3SS genes in Shigella. Finally, we describe the function of translocators and effectors during cell-to-cell spread, particularly during escape from the vacuole, a key element of Shigella’s pathogenesis that has yet to reveal all of its secrets.

Mycoplasma bovis subverts autophagy to promote intracellular replication in bovine mammary epithelial cells cultured in vitro

“…To avoid host autophagic defenses, pathogenic species have developed 3 strategies: evasion, inhibition, and subversion [ 5 , 9 ]. For example, a type III secretion system enables Shigella to avoid being detected by the host autophagic machinery [ 12 ]; Legionella pneumophila inhibits autophagy in mammalian cells [ 30 ]; and Staphylococcus aureus impairs autophagy for replication [ 28 , 31 ]. Similarly, Mycoplasma pneumoniae induced autophagy in mice [ 14 ], whereas Mycoplasma ovipneumoniae activated autophagy in RAW 264.7 cells [ 13 ].…”

“…Furthermore, some of these pathogens have developed strategies to circumvent autophagy or to use it to establish replicative niches within various cell types [ 9 , 10 ]. For example, autophagy benefits several bacterial pathogens, including Salmonella and Legionella, although it is an effective defense mechanism inhibiting survival of Mycobacterium tuberculosis in host cells [ 5 , 11 , 12 ]. For Mycoplasma species, which are the smallest prokaryotes capable of self-replication, autophagy has an important role in host–pathogen interactions.…”

Single domain antibodies against enteric pathogen virulence factors are active as curli fiber fusions on probiotic E. coli Nissle 1917

“…Flagella, which are flexible and extend 5-20 μm from the surface of E. coli , should be more easily bound by curli-displayed VHHs than structures closely associated with the microbial surface, where binding may be sterically constrained [58]. We next tested EcN expressing VHHs targeting Type III secretion systems (T3SSs), which extend less than 50 nm from the outer membrane of Gram-negative bacteria [59], for binding and pathogen neutralization.…”

BipD of Burkholderia pseudomallei: Structure, Functions, and Detection Methods

“…Bsa comprises the structural components of the apparatus (the basal body spans both bacterial membranes, and an extracellular needle protrudes from the bacterial surface) as shown in Figure 1 , secreted proteins (translocators and effectors), chaperones, and cytoplasmic regulators [ 42 ]. Similarly to its Salmonella and Shigella homologs, Bsa follows the inside-out model for its assembly [ 43 ].…”