Genome-Wide Identification of Host Genes Required for Toxicity of Bacterial Cytolethal Distending Toxin in a Yeast Model

Conclusion: The genome-wide screen in the yeast deletion library allowed us to identify a large number of host genes required for AaCdtB cytotoxicity. Further investigation could lead to more insights into the mechanisms of CdtB intoxication. Introduction Bacterial pathogens often possess several virulence factors to facilitate colonization and survival in hosts. Cytolethal distending toxin (CDT) is a genotoxin produced by many Gram-negative pathogens, such as Escherichia coli, Aggregatibacter actinomycetemcomitans, Haemophilus ducreyi, Shigella dysenteriae, Helicobacter hepaticus, and Campylobacter species (Gargi et al., 2012; Taieb et al., 2016). CDT induces DNA damages that lead to cell cycle arrest, cellular distension, and cell death in several cell types (Ohara et al., 2004b; Smith and Bayles, 2006; Fais et al., 2016). In particular, lymphocytes undergo rapid apoptosis upon exposure to CDT (Ohara et al., 2004a). Thus, CDT may contribute to pathogenesis by serving as a mechanism for immune evasion, tissue damage, inflammation, and in some cases, carcinogenesis (Fais et al., 2016). Aggregatibacter actinomycetemcomitans (Aa) is a periodontal pathogen frequently associated with aggressive periodontitis and produces many virulence factors, including CDT (Herbert et al., 2016). It has been shown that AaCDT could damage gingival and periodontal cells and can induce inflammatory responses (Belibasakis et al., 2004, 2005a,b; DiRienzo, 2014a). Clinical isolates of Aa hav...
Source: Frontiers in Microbiology - Category: Microbiology Source Type: research