Posted on | CategoriesDrug Discovery / Pathology | PI: Matthew A. Mulvey, PhD & Jessica C. Brown, PhD

Generation and Treatment of Antibiotic Resistance

Antibiotics are responsible for the most significant increase in lifespan in human history. However, microbes are becoming resistant to antibiotics at an alarming rate. The Mulvey lab found that microbes within a single colonized site, such as the human bladder, can pass antibiotic resistance genes back and forth, propagating resistance as the infecting microbes evolve in response to serial antibiotic treatment. Continue reading → Generation and Treatment of Antibiotic Resistance

Research Statement

My lab’s goal is to explain why the complex network of interactions between a host and an opportunistic pathogen only sometimes results in a stable infection. I primarily use the fungus Cryptococcus neoformans as a model system. C. neoformans causes ~1 million infections and 600,000 deaths annually, most of which occur in patients with a compromised immune system. Despite near universal environmental exposure to C. neoformans, the vast majority of people do not exhibit any adverse health consequences. When C. neoformans does cause disease, it is extremely difficult to treat, commonly causing meningoencephalitis and requiring a year or more on toxic anti-fungal medications.

We investigate the infection process from the perspective of both the fungus and the host, including how C. neoformans interacts with and evades destruction by the host immune system. We are also identifying the genes which allow the fungus to be virulent and discovering their molecular mechanisms of action. Many of these genes are poorly conserved in traditional model organisms, so their characterization opens broad new opportunities to understand immunity and to design targeted, less toxic anti-fungal drugs.

Some of our research questions will include:

1) How does C. neoformans escape from its initial site of infection in the lungs and spread to the brain? What fungal and host genes are involved and how do the gene products interact?

2) How are the cell surface polysaccharides of C. neoformans involved in immune system evasion? How is the mix of these polysaccharides regulated? Are these pathways pathogen-specific, and can pathway members serve as drug targets?

We take an interdisciplinary approach spanning genetics, cell biology, microscopy, genomics, whole genome sequencing, gene expression analysis, and molecular biology in microbial culture, cell culture, and mouse infection model systems. The ultimate goal is to apply our biological knowledge to additional pathogenic fungi and facilitate new anti-fungal therapy development.

Jessica Brown Lab