Department of Microbiology, Nippon Dental University School of Life Dentistry at Tokyo, 1-9-20 Fujimi, Chiyoda-ku, Tokyo 102-8159, Japan.
FEMS Microbiol Lett. 2019 Aug 1;366(16). doi: 10.1093/femsle/fnz204.
Chronic periodontitis is caused by dysbiosis of human oral commensals and especially by increase in Porphyromonas gingivalis. Inhibitors of P. gingivalis growth are expected to serve as effective drugs for the periodontal therapy. 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 Globulin-Albumin (GA) and the newly developed Lactalbumin-Ferric chloride (LF) and Globulin-Calcium chloride (GC); 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 100 000 compounds and identified 73 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.
慢性牙周炎是由人类口腔共生体的失调引起的，尤其是由牙龈卟啉单胞菌的增加引起的。牙龈卟啉单胞菌生长的抑制剂有望作为牙周治疗的有效药物。在本研究中，我们使用牙龈卟啉单胞菌的最小培养基分离了新的牙龈卟啉单胞菌生长抑制剂。最小培养基包括先前报道的球蛋白-白蛋白（GA）和新开发的乳白蛋白-氯化铁（LF）和球蛋白-氯化钙（GC）；所有这些都支持野生型牙龈卟啉单胞菌的生长，但不支持一种缺失 IX 型分泌系统的突变体的生长。GC 含有 CaCl2，表明牙龈卟啉单胞菌的生长需要钙离子。使用 LF 和 GA，我们筛选了大约 100000 种化合物，鉴定出 73 种强烈抑制牙龈卟啉单胞菌生长的化合物。如果我们的筛选中没有使用这些最小培养基，就不会得到这些候选物中的一半以上。我们的候选抑制剂之一是二苯并碘鎓（DPIC），它对牙龈卟啉单胞菌表现出强烈的杀菌活性。黄素腺嘌呤二核苷酸或黄素单核苷酸的过量会抑制 DPIC 的抑制活性，表明 DPIC 将是一种新型有效的生长抑制剂。
