A screening system using minimal media identifies a flavin-competing inhibitor of Porphyromonas gingivalis growth.

Chronic periodontitis is caused by dysbiosis of human oral commensals, and especially by increases in Porphyromonas gingivalis. Inhibitors of P. gingivalis growth are expected to serve as effective drugs for curing this disease. In the present study, we isolated new growth inhibitors of P. gingivalis using minimal media for P. gingivalis. The minimal media included the previously reported GA (Globulin-Albumin) and the newly developed LF (Lactalbumin-Ferric chloride) and GC (Globulin-Calcium chloride); all supported growth of the wild-type strain of P. gingivalis but did not support the growth of a mutant defective for a type IX secretion system. GC contains CaCl2, indicating that P. gingivalis requires a calcium ion for growth. Using LF and GA, we screened about one hundred thousand compounds and identified seventy-three that strongly inhibited the growth of P. gingivalis. More than half of these candidates would not have been obtained if these minimal media had not been used in our screen. One of our candidate inhibitors was diphenyleneiodonium chloride (DPIC), which showed strong bactericidal activity against P. gingivalis. Excess amounts of flavin adenine dinucleotide or flavin mononucleotide suppressed the inhibitory activity of DPIC, suggesting that DPIC would be a novel potent growth inhibitor.