Brian Peters, PhD, First Tennessee Endowed Chair of Excellence in Clinical Pharmacy and professor in the Department of Clinical Pharmacy and Translational Science at the UT Health Science Center, was recently awarded $3.9 million from the National Institute of Allergy and Infectious Diseases for a project aimed at unravelling intricate mysteries surrounding complex fungal-bacterial infections.
James Cassat, MD, PhD, Vanderbilt University Medical Center, and Paul Fidel, PhD, LSU Health New Orleans, are also principal investigators.
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Infections caused by both fungi and bacteria are on the rise among hospital patients, yet there is a significant lack of research addressing these types of infections.
Hospital-related bloodstream infections
Candida albicans, a leading cause of severe fungal infections, ranks among the most common causes of hospital related bloodstream infections in the U.S. Alarmingly, these fungal infections have a higher mortality rate compared to bacterial infections, with approximately 40% of infected individuals not surviving when the fungus enters the bloodstream, despite appropriate treatment.
The situation is even more dire for intra-abdominal infections involving both fungi and bacteria, where mortality rates can soar to 50-75%, far surpassing the 20% mortality associated with bacteria-only infections. Additionally, fungal involvement is linked to increased relapse rates and more severe disease presentation.
Despite the serious implications, the underlying mechanisms that contribute to this heightened mortality remain largely unexplored. The overarching objective of this project aim to uncover the factors within both the body’s defense system and the microbes themselves that contribute to the increased lethality of these dual infections.
Jockeying for space and nutrients
“Despite knowing that microbes exist as diverse communities, pathogenesis-related research is still largely studied using microbes in isolation due to reduced complexity,” Dr. Peters said. “The rules quickly change when suddenly two microbes are jockeying for space and nutrients, which can ultimately alter how they interact with the host. Our multidisciplinary team, with expertise in fungal pathogenesis, bacterial virulence, and immunology is poised to tackle these difficult questions.”
The research team hypothesizes that intra-abdominal infections involving both fungi and bacteria create a lethal environment through microbial interactions that enhance bacterial toxin production. This surge in toxins elicits an exaggerated immune response, disrupts the blood clotting process, and alters bone marrow function that can otherwise confer protection.
To test this hypothesis, the team will model the interactions between Candida albicans (the fungus) and Staphylococcus aureus (a common bacterium associated with such infections). They will investigate how Candida albicans stimulates Staphylococcus aureus to produce increased levels of toxins during co-infection in the abdominal cavity.
Control of bleeding
Another aim is to identify the bacterial factors that impair the body’s ability to control bleeding and form clots during these mixed infections, and how these factors contribute to elevated mortality rates.
Finally, they will explore how the toxins released by Staphylococcus aureus, prompted by Candida, impact bone marrow health and the body’s initial protective immune responses.
Through this research, the team hopes to reveal new mechanisms that underlie the severity of polymicrobial infections and ultimately develop improved therapeutic strategies to enhance treatment outcomes.
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