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.