Mechanistic and genomic insights on the stress responses of Hyphomicrobiales pathogens

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Bacterial pathogens cause disease in plants, animals, and people because they readily evade host immune systems and have evolved mechanisms to survive in a host. Many bacterial pathogens also survive and thrive outside of a host, where they experience environmental stressors similar to those encountered in the host. Pathogens in the Hyphomicrobiales family are stress-resilient and readily transition between different environments, such as Agrobacterium tumefaciens, a phytopathogen, Bartonella hensale, a vectorborne pathogen, and Brucella abortus, a zoonotic pathogen. This dissertation investigates the effects and responses of A. tumefaciens and B. abortus to diverse stress conditions. In A. tumefaciens, functional genomics, forward and reverse genetic approaches, and phenotypic characterization reveal both distinct and shared gene functions that are essential and influential in an array of stress conditions including acidity, b-lactam antibiotics, antimicrobial peptides, hydrogen peroxide, peptide-rich complex media, and liquid and solid media. Remarkably, we find that many individual stress conditions lead not only to stress-specific responses but also to global stress responses which are broadly protective against oxidative, antibiotic, and osmotic stress. Finally, we provide a functional genomic dataset in B. abortus that enables comparisons of stress response genes between these two pathogens, which can help identify shared mechanisms of stress-resilience and virulence. Overall, this dissertation details nuanced, complex regulatory pathways and cellular responses that promote survival in stress resilient pathogens.

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