- Name: Amy E. Bryant, Ph.D.
- Institution: Idaho State University
- Department: Department of Biological and Pharmaceutical Sciences / Meridian
- Phone: 208-373-1928
- Email: firstname.lastname@example.org
Summary: Our work investigates the host/pathogen interactions that mediate rapidly progressive, life-threatening necrotizing infections caused by Gram positive bacteria, including group A streptococcus (“the flesh-eating bacterium”), drug resistant Staphylococcus aureus (“the superbug”) and various species of clostridia involved in gas gangrene. Streptococcal Myonecrosis: We have recently begun to unravel the mystery behind the development of severe group A streptococcal (GAS) infections that occur at sites of minor muscle injuries that do not break the skin (such as a muscle strain). We have identified skeletal muscle vimentin as the principal host ligand that binds invasive strains of GAS. Using a unique animal model combining muscle injury with GAS bacteremia, we have shown that minor muscle injury is sufficient to initiate infection at the injured site and that non-steroidal anti-inflammatory drugs (NSAIDs, such as ibuprofen) greatly enhance this process. We are pursuing the cellular and molecular mechanisms responsible for the NSAID effect and are testing the efficacy of novel therapeutic strategies targeting the vimentin molecule. In addition, we are using this model to develop a novel diagnostic tool that can distinguish between muscle injury alone versus muscle injury complicated by GAS infection. Lastly, we are testing novel therapeutic agents for efficacy in treating established GAS infection. INBRE students could participate in these studies at many levels. Gas Gangrene: We have delineated the molecular mechanisms by which main exotoxin from Clostridium perfringens stimulates intravascular aggregation of platelets and neutrophils that block blood flow and contribute to the rapid destruction of healthy tissue that is so characteristic of clostridial gas gangrene. Our findings suggest that this mechanism is uniquely different from the physiologic mechanisms employed to maintain hemostasis following vessel injury. This implies that pathway-focused therapeutic strategies could prevent vascular occlusion, maintain tissue perfusion and reduce the need for amputation in patients with this devastating infection. INBRE students could help to confirm these findings by examining the effects of pathway-specific blockade on toxin-induced platelet activation. Methicillin-resistant S. aureus: We have shown that sub-inhibitory concentrations of beta lactam antibiotics (like penicillin) induce and prolong toxin gene expression in some Gram positive pathogens. This finding has extremely important clinical ramifications when physicians are choosing treatments for severe infections caused by toxin-producing organisms, such as methicillin-resistant S. aureus (MRSA). We are using a variety of genetic and immunologic approaches to define the mechanisms involved. In all cases, the goal is to translate our understanding of the molecular pathogenesis of these infections into novel forms of treatment that will reduce the incidence and severity of these devastating infections.
Minimum Classes: Cell biology, intro to microbiology
Projects: INBRE students can participate in many different aspects of ongoing projects in my laboratory, including: 1). Investigating the mechanisms by which NSAIDs increase the binding of GAS to injured muscle. This would involve in vitro testing in cell culture and in animal models of injury and infection. 2). Investigating the mechanisms by which NSAIDs predispose to more severe GAS infection. This would involve in vitro testing of the effects of NSAIDs on immune cell function, including phagocytosis, cytokine/chemokine production. 3). Isolation and identification of the vimentin binding adhesin on the surface of group A streptococcus. This would involve a variety of in vitro microbiologic, immunologic, genetic and biochemical techniques. 4). Utilization of microarray technology or quantitative RT-PCR to determine the effects of antibiotic or NSAID exposure on the transcriptomes of antibiotic-sensitive and –resistant GAS.