Research Description The Guttman lab focuses on deciphering how bacteria adapt to, and manipulate their hosts. We study questions related to the evolution of bacterial host specificity and virulence, how pathogen populations and communities (i.e. microbiomes) adapt to the host environment over the course of disease development, and how secreted pathogen effectors evolve and interact with the immune system to determine the outcome of host-microbe interactions. I am particularly fascinated by the scope and impact of natural genetic diversity on these interactions. We use a multidisciplinary approach that harnesses evolutionary genetics, genomics, molecular biology, microbiology, plant biology, pathology, bioinformatics, and statistical genetics to gain insight into how pathogen evolution influences the outcome of host-pathogen interactions. There are two big research directions in the Guttman lab. The first is focuses on understanding the basis of pathogen host specificity. We study how evolutionary processes drive the diversification of pathogenic bacterial strains, and identify host specificity factors and study how these factors evolve and interact with the host immune system to either promote pathogenesis or trigger the immune response. This project is focused on the plant pathogen Pseudomonas syringae, which is a highly diverse species complex consisting of many specialized strains that cause important diseases on nearly all major crops. We are particularly interested in how the type III secreted effector proteins of this species determine the course and fate of the disease process. The second focus centers on human lung pathogens, with an emphasis on the opportunistic pathogen Pseudomonas aeruginosa, which causes numerous drug-resistant, hospital-associated infections, and is the leading cause of death in Cystic Fibrosis patients. These projects primarily focus on understanding how bacterial pathogens evolve over very short time-scales in response to changes in the clinical state or treatment of patients. We want to understand the source of genomic diversity in these populations, how this diversity enables clones to respond to selective pressures imposed by antimicrobial treatments or competition with other species in the microbiome, and novel ways to use this diversity to predict antimicrobial susceptibility and clinical outcomes. Our work is leading to a better understanding of where the genetic potential for virulence originates, how this potential is maintained in bacterial populations, and how pathogen evolution impacts the fitness of their eukaryotic hosts.