The Wu lab is focused on understanding the molecular basis of fusobacterial pathogenesis
1) To understand the molecular basis for Fusobacterium nucleatum-mediated coaggregation and related signal transductions.
Fusobacterium nucleatum is an oral pathobiont not only associated with periodontitis, but also with extra-oral disease such as preterm birth and colorectal cancer. Our current study is focused on understanding the regulations that control F. nucleatum-mediated coaggregation. Coaggregation is the formation of aggregates caused by cell-to-cell recognition of genetically distinct bacteria via the interactions between adhesins and their cognate complementary receptors; it is an important driving force for multispecies biofilm formation in nature. F. nucleatum is a prominent colonizer in dental plaque and has an outstanding coaggregation ability. F. nucleatum exhibits coaggregation with nearly all tested oral bacteria. Because of this, F. nucleatum has been proposed as a bridge microorganism in dental plaque by virtue of its coaggregation with early and late colonizers. In the past decades, intensive work has been done to find which bacteria can aggregate with F. nucleatum and which adhesins in F. nucleatum are responsible for their coaggregation. Studies of coaggregation have so far yielded four fusobacterial adhesins: FomA, Fap2, CmpA and RadD. Of these, FomA and Fap2 bind Porphyromonas gingivalis, CmpA binds a specific Streptococcus strain, and RadD, a versatile adhesin, mediates fusobacterial aggregation with many early and late colonizers, including Aggregatibacter actinomycetemcomitans. We are currently working to determine how the amount and activity of RadD are regulated and how fusobacterial cells sense RadD-directed aggregation and subsequently adjust its physiology to better coexist with its partners in polymicrobial biofilm. We are also interested in how a lysine-sensed riboswitch element in a nice-gene-operon encoding lysine-degrading enzymes complex controls lysine utilization in F. nucleatum.
2) To understand the role of type IV secretion system in pathogeneses of Fusobacterium necrophorum and F. nucleatum.
Fusobacterium necrophorum is a bacterial species responsible for Lumiere’s syndrome. And it has been recently identified as a key cause of persistent sore throat syndrome. Moreover, F. necrophorum associates with several types of cancers. The type IV secretion system is an important “weapon” used by many Gram-negative pathogens bacteria to deal with their hosts and other bacteria. Interestingly, some strains of F. necrophourm and F. nucleatum can express functional Type IV secretion machines. We are interested in the role of the type IV secretion system in fusobacterial pathogenesis.