Type II Toxin Antitoxin ( Ta ) Systems

770 WordsOct 1, 20154 Pages
Type-II toxin-antitoxin (TA) systems are a relatively ubiquitous feature of prokaryotic genomes (1), consisting of a ribonucleolytic toxin and a labile antitoxin. Under normal conditions, the toxin is silenced by pairing with its cognate antitoxin, but can impact cell physiology in several ways when the antitoxin is removed through proteolytic degradation. TA systems were first identified as assisting in plasmid maintenance via post-segregational killing (2,3), as well as in phage exclusion, where expression of the toxin sacrifices some infected cells to preserve the larger population (4). Subsequently, the identification of chromosomal TA systems led to a re-evaluation of their physiological significance, including their potential role in various stress response mechanisms (5) and stochastic persistence (particularly of pathogens) (6). Virulence-associated proteins (Vaps) are a particular class of type-II TA systems characterized by a bi-cistronic locus encoding a proteolytically labile antitoxin (VapB), typically followed by a stable toxin (VapC). These proteins were first identified in connection with virulence plasmids in human pathogens, such as Salmonella Dublin (7), but have since been recognized as one of the most predominant forms of type-II toxins, particularly among the archaea (8). A central component of VapC toxin activity is a PIN-domain, occurring within the approximately 100-amino acid sequence, that displays divalent cation-dependent ribonucleolytic

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