Trevor Bush

Lyme Disease, the most prevalent vector-borne illness in North America, stems from B. burgdorferi infection transmitted by ticks. Initial symptoms encompass fever, joint aches, lymph node swelling, and rash. Untreated cases progress to severe manifestations like facial palsy, arthritis, intense headaches, and brain inflammation. With an average of 476,000 cases between 2010 and 2018, Lyme disease poses a significant healthcare challenge. Borrelia burgdorferis BBA64 gene is a surface-localized lipoprotein and its protein H7C7P4 (P35 Antigen) play a crucial role in the trans-mission of B. burgdorferi. Comparing compatibility could aid in identifying antibodies specific to the P35 antigen, potentially enhancing efficacy against transmission. The tools PDB, UniProt KB, T-Coffee, InterPro, UCSF Chimera, and HDOCK were integrated for proteomic analysis of H7C7P4 and structural, sequence, and docking analysis to elucidate the P35 Antigen's characteristics and to propose a novel drug target.

Tuberculosis, caused by Mycobacterium tuberculosis (Mtb), is a deadly and debilitating disease globally affecting millions annually. Emerging drug-resistant Mtb strains endanger the efficacy of the current combination therapies employed to treat tuberculosis; therefore, there is an urgent need to develop novel drugs to combat this disease. Artemisia afra is used traditionally in southern Africa to treat malaria and recently has shown anti tuberculosis activity. This genus synthesizes a prodigious number of phytochemicals, many of which have demonstrated human health effects. Transcriptomic analysis revealed that A. afra exerts different effects on Mtb compared to A. annua or the well-known antimalarial artemisinin, suggesting other phytochemicals present in A. afra with unique modes of action. A biochemometric study of A. afra resulted in the isolation of a methoxylated flavone (1), which displayed considerable activity against Mtb strain mc26230. Compound 1 had an MIC of 312.5 μg/mL and yielded no viable colonies after 6 days of treatment. In addition, 1 was effective in killing hypoxic Mtb cultures, with no viable cultures after 2 days of treatment. This suggested that A. afra is a source of potentially powerful anti-Mtb phytochemicals with novel mechanisms of action.

Fibrosis is a pathological occurrence in most chronic inflammatory and autoimmune diseases where wound healing results in the buildup of non-functional tissue. This process involves the excessive aggregation of extracellular matrix proteins, posing a significant threat of organ failure. Unfortunately, there are few treatments for fibrosis. Most known for its antimalarial activity, artemisinin (ART), from the plant Artemisia annua L. and its derivatives artesunate (AS), artemether (AM), and dihydroartemisinin (DHA) along with A. annua tea infusions are used globally against malaria and other infectious diseases including possibly against fibrosis. The aim here was to determine morphological and extracellular matrix protein changes in fibroblasts during their transition to myofibroblasts post drug treatment. Preliminary growth and qPCR results indicated that not all artemisinin derivatives similarly affected fibroblasts, highlighting the need for further investigation.