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Impact of Salmonella enterica Type III Secretion System Effectors on the Eukaryotic Host Cell

DOI: 10.5402/2012/787934

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Abstract:

Type III secretion systems are molecular machines used by many Gram-negative bacterial pathogens to inject proteins, known as effectors, directly into eukaryotic host cells. These proteins manipulate host signal transduction pathways and cellular processes to the pathogen’s advantage. Salmonella enterica possesses two virulence-related type III secretion systems that deliver more than forty effectors. This paper reviews our current knowledge about the functions, biochemical activities, host targets, and impact on host cells of these effectors. First, the concerted action of effectors at the cellular level in relevant aspects of the interaction between Salmonella and its hosts is analyzed. Then, particular issues that will drive research in the field in the near future are discussed. Finally, detailed information about each individual effector is provided. 1. Introduction: Type III Secretion Systems and Salmonella Gram-negative bacteria have evolved several machineries, known as secretion systems, for transport of substrates across their cell membranes in response to various environmental cues. Secretion of proteins is often essential for pathogenicity, biofilm formation, modulation of the eukaryote host, and nutrient acquisition. There are at least seven different secretion systems classified as type I (T1SS) to type VI (T6SS) and the CU (chaperone-usher) system. Two main mechanisms for transport operate in these secretion systems: the proteins can be exported directly from the cytoplasm out of the cell by a one-step process or by a two-step process where the protein is first exported through the inner membrane to the periplasm and then moved across the outer membrane. The T2SS, T5SS, and the CU transport substrates from the periplasm across the outer membrane. They are classified as two-step translocation pathways as they rely on the general secretory pathway, Sec, or the Tat pathway for the first step of transfer across the inner membrane. T1SS, T3SS, T4SS, and T6SS are one-step transport systems that carry out simultaneous translocation of substrates across both membranes without periplasmic intermediates [1]. Many Gram-negative bacterial pathogens of animals or plants, including members of the genera Salmonella, Shigella, Yersinia, Escherichia, and Pseudomonas, rely on T3SSs to inject proteins directly into the eukaryotic host cells. Substrates of T3SSs, known as effectors, are transported via a flagellum-like injectisome from the cytoplasm of the bacterial cell across the inner and outer membrane to the cytoplasm of a eukaryotic host cell. These

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