Structure and Biophysics of Type III Secretion in Bacteria

ArticleinBiochemistry 52(15):2508–2517 · April 2013with31 Reads
DOI: 10.1021/bi400160a
Abstract
Many plant and animal bacterial pathogens assemble a needle-like nanomachine, the type III secretion system (T3SS), to inject virulence proteins directly into eukaryotic cells to initiate infection. The ability of bacteria to inject effectors into host cells is essential for infection, survival, and pathogenesis for many Gram-negative bacteria, including Salmonella, Escherichia, Shigella, Yersinia, Pseudomonas, and Chlamydia spp. These pathogens are responsible for a wide variety of diseases, such as typhoid fever, large-scale food-borne illnesses, dysentery, bubonic plague, secondary hospital infections, and sexually transmitted diseases. The T3SS consists of structural and nonstructural proteins. The structural proteins assemble the needle apparatus, which consists of a membrane-embedded basal structure, an external needle that protrudes from the bacterial surface, and a tip complex that caps the needle. Upon host cell contact, a translocon is assembled between the needle tip complex and the host cell, serving as a gateway for translocation of effector proteins by creating a pore in the host cell membrane. Following delivery into the host cytoplasm, effectors initiate and maintain infection by manipulating host cell biology, such as cell signaling, secretory trafficking, cytoskeletal dynamics, and the inflammatory response. Finally, chaperones serve as regulators of secretion by sequestering effectors and some structural proteins within the bacterial cytoplasm. This review will focus on the latest developments and future challenges concerning the structure and biophysics of the needle apparatus.
    • "Since the proteins that make up T3SS are highly conserved across many different species of Gram-negative bacteria on their sequences, structures, and functions [61][62][63], we chose T3SS structural proteins of Salmonella typhimurium SPI-1 in this study. The number of T3SS structural proteins in Salmonella was estimated to be around 20 in previous studies [64] . "
    Article · Jan 2016 · Frontiers in Microbiology
    • "Chaperones belong to three different classes: Class I chaperones recognize effectors; class II chaperones interact with translocators; and class III chaperones sequester the needle-forming proteins [18]. The chaperones of the translocon proteins are class II chaperones, and they are responsible for partitioning the intracellular pools of the translocon proteins in order to prevent their premature degradation [12]. Effector proteins travel in an unfolded or partially-folded conformation through the type III secretion channels, and the chaperones may keep the proteins in a secretion-competent conformation, probably by preventing them from folding. "
    [Show abstract] [Hide abstract] ABSTRACT: Drug-resistant pathogens have presented increasing challenges to the discovery and development of new antibacterial agents. The type III secretion system (T3SS), existing in bacterial chromosomes or plasmids, is one of the most complicated protein secretion systems. T3SSs of animal and plant pathogens possess many highly conserved main structural components comprised of about 20 proteins. Many Gram-negative bacteria carry T3SS as a major virulence determinant, and using the T3SS, the bacteria secrete and inject effector proteins into target host cells, triggering disease symptoms. Therefore, T3SS has emerged as an attractive target for antimicrobial therapeutics. In recent years, many T3SS-targeting small-molecule inhibitors have been discovered; these inhibitors prevent the bacteria from injecting effector proteins and from causing pathophysiology in host cells. Targeting the virulence of Gram-negative pathogens, rather than their survival, is an innovative and promising approach that may greatly reduce selection pressures on pathogens to develop drug-resistant mutations. This article summarizes recent progress in the search for promising small-molecule T3SS inhibitors that target the secretion and translocation of bacterial effector proteins.
    Full-text · Article · Sep 2015
    • "The type III secretion systems (T3SSs) are transmembrane apparatuses formed by the multicomponent protein complexes (Cornelis, 2006), that allow effectors or virulence proteins to be injected directly into the cytoplasm of the host cell (Dean, 2011; Chatterjee et al., 2013). There are two different T3SS systems in V. parahaemolyticus, designated T3SS1 and T3SS2 (Makino et al., 2003). "
    [Show abstract] [Hide abstract] ABSTRACT: Vibrio parahaemolyticus, a Gram-negative motile bacterium that inhabits marine and estuarine environments throughout the world, is a major food-borne pathogen that causes life-threatening diseases in humans after the consumption of raw or undercooked seafood. The global occurrence of V. parahaemolyticus accentuates the importance of investigating its virulence factors and their effects on the human host.This review describes the virulence factors of V. parahaemolyticus reported to date, including hemolysin, urease, two type III secretion systems and two type VI secretion systems, which both cause both cytotoxicity in cultured cells and enterotoxicity in animal models. We describe various types of detection methods, based on virulence factors, that are used for quantitative detection of V. parahaemolyticus in seafood. We also discuss some useful preventive measures and therapeutic strategies for the diseases mediated by V. parahaemolyticus, which can reduce, to some extent, the damage to humans and aquatic animals attributable to V. parahaemolyticus. This review extends our understanding of the pathogenic mechanisms of V. parahaemolyticus mediated by virulence factors and the diseases it causes in its human host. It should provide new insights for the diagnosis, treatment, and prevention of V. parahaemolyticus infection.
    Full-text · Article · May 2015
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