Jonathan Dennis, PhD

Area of Study / Keywords

Molecular Microbiology Bacterial Pathogenesis Antibiotic Resistance Bacterial Genetics Bacteriophages Phage Therapy

Research

The Burkholderia cepacia complex (Bcc) is a group of important opportunistic pathogenic bacteria that are responsible for causing devastating infections, numerous epidemics, and a significant amount of mortality, particularly in patients with Cystic Fibrosis (CF) and Chronic Granulomatous Disease. In CF, it can produce a rapidly fatal septicemia termed "cepacia syndrome". Due to the remarkable metabolic capabilities and relatively large, complex genome of this microorganism, B. cepacia strains exhibit tremendous antibiotic resistance. This extreme multidrug resistance has led to a lack of effective antimicrobial therapy. Using genetic and genomic approaches, we are attempting to identify and characterize potential virulence factors and virulence factor genes that are involved in the antibiotic resistance and pathogenesis of the B. cepacia complex.

Because extreme drug resistant (XDR) bacteria such as members of the Bcc are able to withstand treatment with almost all known classes of chemical antibiotics, alternative therapeutic strategies are desperately needed. We are developing the use of bacteriophages (or phages) for the treatment of members of the Bcc. We are also investigating the potential use of "phage therapy" for the treatment of other XDR bacteria. Although the idea of using bacterial viruses to kill pathogenic bacteria has been around for many years, its potential use has only now become more urgent with the recent upswing in extreme antibiotic resistant bacteria, and the lack of new effective chemical antibiotics. The use of phages to treat bacteria has been demonstrated to be safe, highly specific, and effective, both in vitro and in vivo. My lab has extensive experience and expertise in phage isolation from multiple sources, phage characterization (including phage biology, genomic and genetic characterization, and electron microscopy), and phage therapy (including cocktail compilation, animal model development, and modes of delivery, specializing in aerosolization). We are working towards discovering methods to cure patients with XDR bacterial infections utilizing phage therapy, and improving phage therapy efficacy through the development of modified or enhanced phages, using advanced molecular genetics and synthetic biology.

GENET 270 - Foundations of Molecular Genetics

Basic concepts on the organization of genetic material and its expression will be developed from experiments on bacteria and viruses. Prerequisite: BIOL 207.

MICRB 316 - Molecular Microbiology

Factors that affect prokaryotic gene expression at the levels of replication, transcription, post-transcriptional and post-translational control. Topics will include mobile genetic elements and their effect on chromosome structure and gene expression; alternate sigma factors; protein modification and degradation; RNA structure, processing and decay; and DNA modification and rearrangement in gene control. Prerequisites: GENET 270, MICRB 265 and BIOCH 203/205 or BIOCH 200. Note: MICRB 316 and 516 cannot both be taken for credit.

MICRB 516 - Advanced Molecular Microbiology

Lecture course on molecular mechanisms relating to gene expression of prokaryotes based on the current literature. In addition, students will prepare an analytical literature review on a chosen topic relating to this field. Prerequisite: consent of the instructor. Credit cannot be obtained for both MICRB 316 and 516.

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