Mechanism of gene regulation by a Staphylococcus aureus toxin. Staphylococcus aureus

Virulence of many bacterial pathogens, including the important human pathogen Staphylococcus aureus, depends on the secretion of frequently high amounts of toxins. Toxin production involves the need for the bacteria to make physiological adjustments for energy conservation. While toxins are primarily known to be targets of gene regulation, such changes may be accomplished by regulatory functions of the toxins themselves. However, mechanisms by which toxins regulate gene expression have remained poorly understood. We show here that the phenol-soluble modulin toxins have gene regulatory functions, which in particular include regulation of their own export by direct interference with a GntR-type repressor protein. This capacity was most pronounced in PSMs with low cytolytic capacity, demonstrating functional specification among closely related members of that toxin family. Our study presents a paradigmatic example of how bacterial toxins may regulate gene expression to adapt to the physiological needs in situations of enhanced toxin production. Overall design: strain vs. different strain, 3 replicates