We study how animals have evolved to defend against bacterial pathogens, and how bacteria evolve to survive within the host environment.

EVOLUTION OF ANTIMICROBIAL DEFENSES

Infectious diseases are a potent force of natural selection, driving repeated adaptation of host populations. Our lab studies how animals, including humans, have evolved to defend against pathogenic bacteria. Bacterial infections are a leading source of morbidity and mortality around the world, even as resistance to antibiotics continues to spread. Identifying new strategies to treat and prevent bacterial infections is therefore a pressing global health imperative. We apply genetic and genomic approaches to identify patterns of rapid evolution in host defense genes, guiding molecular and cellular experiments to test the functional consequences of host genetic variation.

Our lab previously discovered evidence of rapid adaptation among primate cell surface receptors that mediate pathogen detection (Kohler et al., 2020; Paterson et al., 2021). We have also described how genetic variation of host proteins required for bacterial colonization and growth can lead to changes in host species preference (Barber et al., 2014; Baker et al., 2022). Collectively this work has revealed key barriers to cross-species bacterial transmission, and how these barriers may be overcome during zoonotic disease outbreaks.

BACTERIAL ADAPTATION TO HOST ENVIRONMENTS

Bacteria are faced with a variety of challenges during colonization or infection including nutrient limitation, predatory viruses (phages), competing resident microbes, antibiotics, and host defense molecules. One of our major goals is to determine how pathogenic bacteria evolve to overcome these diverse obstacles within the host. We apply laboratory experimental evolution to track bacterial adaptation in real time, integrating molecular and genetic approaches to test the impact of mutations on pathogenic traits. Our work in this area has focused on the major bacterial pathogen Staphylococcus aureus. This bacterium colonizes a large proportion of the human population asymptomatically, but is also a leading cause of skin and soft tissue infections, pneumonia, sepsis, and other deadly conditions. S. aureus is notorious for its frequent resistance to antibiotics, particularly methicillin resistant S. aureus (MRSA) strains which are among the most common causes of antibiotic-resistant infections globally. We are investigating how S. aureus adapts to distinct challenges encountered in the host environment, including competing microbes, host defense factors, and phage predation, as well as how bacterial evolution impacts virulence traits and antibiotic susceptibility. Identifying determinants of adaptation in human pathogens like S. aureus could ultimately reveal new avenues for infectious disease treatment and prevention.