In partial fulfillment of the requirements for the degree of
Doctor of Philosophy in Bioinformatics
in the School of Biological Sciences
Benjamin Metcalf
Defends his thesis:
The Interrelationship Between Bacterial and Societal Factors Drives Pneumococcal Transmission and Disease Progression
Wednesday, May 1, 2024
2:00pm
BME Whitaker building, Room 1214
Thesis Advisor:
Dr. Sam Brown, Advisor
School of Biological Sciences
Georgia Institute of Technology
Co-Advisor:
Dr. Kristofer Wollein Waldetoft, Co-Advisor
School of Biological Sciences
Georgia Institute of Technology
Committee Members:
Dr. Marvin Whiteley
School of Biological Sciences
Georgia Institute of Technology
Dr. Joshua Weitz
Previous Affiliation: School of Biological Sciences
Georgia Institute of Technology
Current Affiliation: School of Biology
University of Maryland
Dr. Joe Lachance
School of Biological Sciences
Georgia Institute of Technology
Dr. Bernard Beall
Division of Bacterial Diseases
Centers for Disease Control and Prevention
Abstract:
Streptococcus pneumoniae (Spn) is a gram-positive opportunistic pathogen and a leading cause of bacterial pneumonia, meningitis, and sepsis worldwide. Spn is typically categorized by serotype and in most cases colonizes the nasopharynx asymptomatically (defined as carriage). On rare occasions, it can spread into normally sterile sites and cause severe infections known as invasive pneumococcal disease (IPD). Both the ability of Spn to cause these life-threatening illnesses (i.e., its invasiveness) and the length of time in carriage (i.e., its carriage duration) vary substantially across serotypes. IPD cases can occur in isolation or, occasionally, spread as localized outbreaks, often arising within disadvantaged communities like people experiencing homelessness (PEH) and people who inject drugs (PWID). In this dissertation, we seek to explore how pneumococcal life-history traits, host demographic factors, and the interrelationships between them can impact invasive disease at the population level.
In Chapter Two we show that variation in carriage duration can confound serotype invasiveness measurements and identify the best performing metrics for invasiveness. Our results also support previous work showing that when invasion occurs, it does so at or near the time of carriage acquisition. In Chapter Three we show that Spn transmission is host density-dependent, resulting in a stratification of serotypes by human population density. The fourth chapter provides evidence that the risk of IPD and IPD clustering is in part governed by human social conditions, with increased risks in disadvantaged populations. In the final discussion chapter, we provide a broader discussion of potential future directions of research, building on the work in this thesis.
