ISS: Exploiting the Space Environment to Dissect the Molecular Basis of Streptococcus pneumoniae (Spn) Cardiotoxicity”

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Streptococcus pneumonia (Spn), a Gram-positive bacterium is the leading cause of community-acquired pneumonia. During severe community-acquired pneumonia, Spn enters and causes long-lasting damage in vital organs such as the heart. Despite the use of antibiotics to treat the pneumonia, a large number of these patients are still at risk for heart disease. Current knowledge confirms that Spn can infect the heart and establish biofilms within the heart muscle, resulting in cell death and muscle dysfunction. However, there is still an incomplete understanding of critical factors that allow Spn to overcome treatment with antibiotics and cause damage in the heart. In this project, a Cardiac Tissue Chip (CTC) model will be used to study Spn infections. The space environment (which has been shown to worsen bacterial infections) will enable the researchers to clearly identify important factors that play a role in this process to identify new treatment options. This project will also provide multi-disciplinary training opportunities for 1 graduate student, 2 undergraduate students and 2 high school students. The undergraduate students will be recruited via UABs PARAdiGM program (Preparation for graduate and medical school), a summer program for undergraduates from disadvantaged and underrepresented minority backgrounds who are keen to explore the potential of a future career as a scientific investigator or medical professional. Research outcomes from this project will be incorporated into modules for two courses focused on stem cell bioengineering and heart failure.The goal of this project is to exploit unique phenomena associated with the space environment to create a model of Spn infection of cardiac tissue to gain an understanding of critical molecular signaling pathways associated with the onset and progression of Spn infections that lead to cardiac tissue dysfunction. In space, multiple factors affect normal tissue and cellular function, such as promoting cardiac tissue atrophy making it more susceptible to bacterial infection. There is also sufficient evidence to suggest that the space environment, particularly microgravity, greatly increases bacterial virulence and diminishes susceptibility to commonly used antimicrobial treatments. This project will leverage the space environment to amplify the effects of Spn infection to more effectively identify molecular changes (gene expression, soluble factor production) involved in critical events that promote Spn cardiotoxicity. Elucidation of molecular mechanisms at play will enable identification of therapeutic targets for early intervention to prevent adverse cardiac events. Successful completion of this project will confirm that the tissue-level and organ-level changes engendered by the space environment accelerate and exacerbate bacterial infection and will yield valuable information regarding: (a) how Spn infection of cardiac tissue is different on earth and in space, (b) molecular mechanisms that promote enhanced virulence and biofilm formation, (c) factors that promote increased drug resistance in space, and (d) identification of potential therapeutic targets for early intervention to prevent adverse cardiac events.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.