RESUMEN
BACKGROUND: Type Three Secretion Systems (T3SS) are nanomachine complexes, which display the ability to inject effector proteins directly into host cells. This skill allows for gram-negative bacteria to modulate several host cell responses, such as cytoskeleton rearrangement, signal transduction, and cytokine production, which in turn increase the pathogenicity of these bacteria. The Salmonella enterica subsp. enterica serovar Typhimurium (ST) T3SS has been the most characterized so far. Among gram-negative bacterium, ST is one of enterica groups predicted to have two T3SSs activated during different phases of infection. OBJECTIVE: To comprise current information about ST T3SS structure and function as well as an overview of its assembly and hierarchical regulation. METHODS: With a brief and straightforward reading, this review summarized aspects of both ST T3SS, such as its structure and function. That was possible due to the development of novel techniques, such as X-ray crystallography, cryoelectron microscopy, and nano-gold labelling, which also elucidated the mechanisms behind T3SS assembly and regulation, which was addressed in this review. CONCLUSION: This paper provided fundamental overview of ST T3SS assembly and regulation, besides summarized the structure and function of this complex. Due to T3SS relevance in ST pathogenicity, this complex could become a potential target in therapeutic studies as this nanomachine modulates the infection process.
Asunto(s)
Salmonella typhimurium/metabolismo , Sistemas de Secreción Tipo III/metabolismo , Salmonella typhimurium/patogenicidad , Salmonella typhimurium/ultraestructura , Sistemas de Secreción Tipo III/químicaRESUMEN
Enteropathogenic Escherichia coli and enterohemorrhagic E. coli are diarrheagenic bacterial human pathogens that cause severe gastroenteritis. These enteric pathotypes, together with the mouse pathogen Citrobacter rodentium, belong to the family of attaching and effacing pathogens that form a distinctive histological lesion in the intestinal epithelium. The virulence of these bacteria depends on a type III secretion system (T3SS), which mediates the translocation of effector proteins from the bacterial cytosol into the infected cells. The core architecture of the T3SS consists of a multi-ring basal body embedded in the bacterial membranes, a periplasmic inner rod, a transmembrane export apparatus in the inner membrane, and cytosolic components including an ATPase complex and the C-ring. In addition, two distinct hollow appendages are assembled on the extracellular face of the basal body creating a channel for protein secretion: an approximately 23 nm needle, and a filament that extends up to 600 nm. This filamentous structure allows these pathogens to get through the host cells mucus barrier. Upon contact with the target cell, a translocation pore is assembled in the host membrane through which the effector proteins are injected. Assembly of the T3SS is strictly regulated to ensure proper timing of substrate secretion. The different type III substrates coexist in the bacterial cytoplasm, and their hierarchical secretion is determined by specialized chaperones in coordination with two molecular switches and the so-called sorting platform. In this review, we present recent advances in the understanding of the T3SS in attaching and effacing pathogens.