Dr. Charles Darkoh
The University of Texas Health Science Center at Houston
School of Public Health
Department of Epidemiology, Human Genetics & Environmental Sciences
Center for Infectious Diseases
My laboratory focuses on microbial pathogenesis, molecular epidemiology, and molecular basis of enteric infectious diseases with the goal to identify and understand the mechanisms of action of novel virulence factors, pathways, and unique microbial products that can be harnessed for diagnostics and therapeutics. My long-term research interests include examining the role of microbially-produced small molecules and metabolites in the pathogenesis of enteric infectious diseases, mechanisms of host-pathogen interactions, antimicrobial resistance, host genetics and susceptibility to bacterial infections, and developing new genetic systems for bacterial pathogenesis studies.
One of the current projects in my laboratory involves elucidating the mechanism of toxin regulation in Clostridium difficile, a multidrug-resistant pathogen responsible for majority of the hospital-acquired and antibiotic-associated diarrhea in the United States with an estimated total cost of treatment between 1 to 4.8 billion U.S. dollars annually. This anaerobic bacterium causes disease by producing toxins. To detect low levels of the toxins, we developed a sensitive assay that measures their enzymatic activity, which we anticipate will one day either replace or augment the current diagnostic methods. With this assay, we have discovered for the first time that C. difficile regulates the production of its disease-causing toxins using a unique small quorum-signaling cyclic peptide, which is released by the infecting bacteria and accumulates in the colon during infection. Furthermore, my laboratory has identified the novel pathway in C. difficile that is responsible for producing the cyclic peptide important for the production of its toxins. This has enabled us to identify novel compounds that block the pathway and hence, toxin production. We have also identified another group of compounds that inhibit toxin activity. These discoveries together, offer exciting new avenues both for rapid detection of C. difficile infections and development of novel non-antibiotic therapies for the treatment of both initial and recurrent C. difficile infections. A long-term goal of my laboratory is to understand all of the players and mechanisms involved in C. difficile toxin regulation, which I anticipate will allow us to develop novel therapeutics to combat this life-threatening emerging multidrug-resistant pathogen.
A tutorial student in my laboratory will gain experience working with both aerobic and anaerobic clinical pathogens, animal models of enteric infection, learn various molecular biology, microbial genetics, and biochemical techniques in a translational research setting.