Discovery of a novel mechanism in coagulase-negative staphylococci for inhibition of Staphylococcus aureus growth and virulence

We discovered that Staphylococcus chromogenes ATCC43764, the type strain for the species, synthesizes and secretes 6-thioguanine (6-TG), a purine analog that suppresses growth of S. aureus in liquid and on solid growth media. Growth inhibition by 6-TG was exacerbated when S. aureus was purine starved, as 6-TG inhibits de novo purine biosynthesis. The S. chromogenes 6-TG biosynthetic gene cluster was identified and cloned into S. aureus, enabling S. aureus to synthesize and secrete 6-TG into the culture supernatant. Prophylactic treatment of subcutaneous skin infections in mice with 6-TG drastically reduced necrotic skin lesions, likely due to the profound ability of 6-TG to abrogate toxin secretion by S. aureus.