The underlying theme of Dr. David J. Kolodrubetz's research is to develop and use molecular genetic, genomic and biochemical approaches to elucidate the functions and regulation of virulence factors in periodontal pathogens. We have identified and are characterizing three proteins that constitute a novel pathway which regulates the transcription of leukotoxin, and possibly other virulence factor genes, in Aggregatibacter actinomycetemcomitans.
We recently started a project to prove that lysine de-acetylation of transcription factors by CobB, an NAD+-dependent deacetylase, modulates global A. actinomycetemcomitans transcription in response to altered cellular physiology (NAD levels). Finally, we are collaborating with Dr. L. Chu to show that T. denticola metabolism causes decreased glutathione levels and increased H2S production in subgingival pockets, leading to the host tissue damage seen in periodontal disease.
Chu L, Lai Y, Xu X, Eddy S, Yang S, Song L, Kolodrubetz D. A 52-kDa leucyl aminopeptidase from treponema denticola is a cysteinylglycinase that mediates the second step of glutathione metabolism. J Biol Chem. 2008 Jul 11;283(28):19351-8.
Kolodrubetz D, Phillips L, Burgum A. Repression of aerobic leukotoxin transcription by integration host factor in Aggregatibacter actinomycetemcomitans. Res Microbiol. 2010 Sep;161(7):541-8.
Feuerbacher LA, Burgum A, Kolodrubetz D. The cyclic-AMP receptor protein (CRP) regulon in Aggregatibacter actinomycetemcomitans includes leukotoxin. Microb Pathog. 2011 Sep;51(3):133-41.
Childress C, Feuerbacher LA, Phillips L, Burgum A, Kolodrubetz D. Mlc is a transcriptional activator with a key role in integrating cyclic AMP receptor protein and integration host factor regulation of leukotoxin RNA synthesis in Aggregatibacter actinomycetemcomitans. J Bacteriol. 2013 May;195(10):2284-97.