A Cytolethal Distending Toxin Variant from <i>Aggregatibacter actinomycetemcomitans</i> with an Aberrant CdtB That Lacks the Conserved Catalytic Histidine 160

<div><p>The periodontopathogen <i>Aggregatibacter actinomycetemcomitans</i> synthesizes several virulence factors, including cytolethal distending toxin (CDT). The active CDT holoenzyme is an AB-type tripartite genotoxin that affects eukaryotic cells. Subunits CdtA and CdtC (B-components) allow binding and intracellular translocation of the active CdtB (A-component), which elicits nuclear DNA damage. Different strains of <i>A</i>. <i>actinomycetemcomitans</i> have diverse virulence genotypes, which results in varied pathogenic potential and disease progression. Here, we identified an <i>A</i>. <i>actinomycetemcomitans</i> strain isolated from two patients with advance chronic periodontitis that has a regular <i>cdtABC</i> operon, which, however, codes for a unique, shorter, variant of the CdtB subunit. We describe the characteristics of this CdtBΔ116–188, which lacks the intact nuclear localisation signal and the catalytic histidine 160. We show that the <i>A</i>. <i>actinomycetemcomitans</i> DO15 isolate secretes CdtBΔ116–188, and that this subunit cannot form a holotoxin and is also not genotoxic if expressed ectopically in HeLa cells. Furthermore, the <i>A</i>. <i>actinomycetemcomitans</i> DO15 isolate is not toxic, nor does it induce cellular distention upon infection of co-cultivated HeLa cells. Biological significance of this deletion in the <i>cdtB</i> remains to be explained.</p>