Date of Award

Fall 12-15-2023

Level of Access Assigned by Author

Open-Access Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Biomedical Sciences

Advisor

Melody N. Neely

Second Committee Member

Robert T. Wheeler

Third Committee Member

Sally D. Molloy

Additional Committee Members

Joshua Kelley

Gregory Cox

Abstract

Streptococcus agalactiae (Group B Streptococcus or GBS), a Gram-positive bacterium, and Candida albicans, a polymorphic fungus, are commensal microbes in most of the population they colonize but are also capable of causing severe and sometimes fatal infections in certain patient groups. Both organisms share similarities including the colonization the same tissue environments and causing infections in specific patient groups including those who are newborn, pregnant, suffering from chronic conditions like diabetes and HIV, as well as elderly patients. Previous research discovered that GBS and C. albicans can synergize to enhance the colonization of GBS in the bladders of mice, but besides this not much was known prior to the research in this dissertation about how interactions between these two infectious pathogens can alter infection or treatment effectiveness in co-infected hosts. This dissertation aimed to determine if interactions between these two organisms can alter their viability, ability to withstand antimicrobial challenge, as well as influence their virulence in co-infections compared to solo infection. We discovered that interactions between the two opportunistic pathogens were influenced by media nutrient availability and pH, and that the presence of C. albicans in a culture reduces the effectiveness of certain antibiotics against GBS in vitro. We also utilized a larval zebrafish model to investigate differences in virulence in solo infection vs co-infections in vivo. Zebrafish co-infected with GBS and C. albicans had decreased survival rates compared to solo infections of either pathogen depending on the initial infection route. Co-infection also led to an increased GBS burden compared to solo GBS infections. The antibiotic clindamycin was also less effective at reducing mortality rates in co-infected zebrafish compared to zebrafish infected with just GBS, indicating that C. albicans may make the antibiotic clindamycin less effective against GBS in vivo. Overall, these findings highlight how interactions between GBS and C. albicans can influence treatment effectiveness and virulence. This is clinically relevant, as polymicrobial interactions are not often considered when choosing treatment options for patients infected with a microbe, and polymicrobial interactions like what we have identified in this dissertation may be influencing infection and treatment outcomes in patients.

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