Bacterial diseases kill millions of people worldwide each year, despite the advent of antibiotics 90 years ago. Emergence and spread of new and rapidly evolving pathogens with increased virulence, resistance to antibiotics, and transmissibility is increasingly straining efforts to manage infections and save lives. To combat this trend, we need a comprehensive and systematic understanding of the complex dynamics between the host, including host microbiota, and pathogen at every level of interaction?cellular, individual, and population levels. Our proposed studies leverage recent advances in sequencing technologies, innovative high-throughput molecular and multi-omic approaches, access to unique patient cohorts, and novel computational methods to characterize the genomes, transcriptomes, and individual strain-level interactions of bacterial pathogens with their hosts and other microbiota. In collaboration with renowned infectious disease researchers, clinicians, and epidemiologists, we will target critical gaps in our understanding of key infectious disease threats?uropathogenic E?scherichia coli (UPEC), carbapenem resistant ?Enter?obacteriaceae (CRE), and multidrug resistant enterococci. Specifically, we will i)? ?determine the gut-to-urinary tract dynamics of UPEC in recurrent urinary tract infections; ii) track the multiscale dynamics of antibiotic resistance gene proliferation - from individual microbiota to local and global circulation; and iii) characterize the dynamic functional reservoir of MDR enterococci. While our aims focus on ESKAPE pathogens, our goal is to pioneer and disseminate a ?comprehensive? ?technological framework and resources to empower clinical and research communities working to understand, diagnose, prevent, and treat infectious diseases.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Program--Cooperative Agreements (U19)
Project #
2U19AI110818-06
Application #
9729352
Study Section
Special Emphasis Panel (ZAI1)
Project Start
Project End
Budget Start
2019-04-23
Budget End
2020-03-31
Support Year
6
Fiscal Year
2019
Total Cost
Indirect Cost
Name
Broad Institute, Inc.
Department
Type
DUNS #
623544785
City
Cambridge
State
MA
Country
United States
Zip Code
02142
Messina, Julia A; Wolfe, Cameron R; Hemmersbach-Miller, Marion et al. (2018) Genomic characterization of recurrent mold infections in thoracic transplant recipients. Transpl Infect Dis 20:e12935
Schaffner, Stephen F; Taylor, Aimee R; Wong, Wesley et al. (2018) hmmIBD: software to infer pairwise identity by descent between haploid genotypes. Malar J 17:196
Farrer, Rhys A; Ford, Christopher B; Rhodes, Johanna et al. (2018) Transcriptional Heterogeneity of Cryptococcus gattii VGII Compared with Non-VGII Lineages Underpins Key Pathogenicity Pathways. mSphere 3:
Myhrvold, Cameron; Freije, Catherine A; Gootenberg, Jonathan S et al. (2018) Field-deployable viral diagnostics using CRISPR-Cas13. Science 360:444-448
Cuomo, Christina A; Rhodes, Johanna; Desjardins, Christopher A (2018) Advances in Cryptococcus genomics: insights into the evolution of pathogenesis. Mem Inst Oswaldo Cruz 113:e170473
Manson, Abigail L; Abeel, Thomas; Galagan, James et al. (2018) Reply to Lee and Howden. Clin Infect Dis 66:160-161
Donaldson, G P; Ladinsky, M S; Yu, K B et al. (2018) Gut microbiota utilize immunoglobulin A for mucosal colonization. Science 360:795-800
Fernandes, Kenya E; Brockway, Adam; Haverkamp, Miriam et al. (2018) Phenotypic Variability Correlates with Clinical Outcome in Cryptococcus Isolates Obtained from Botswanan HIV/AIDS Patients. MBio 9:
Muñoz, José F; Gade, Lalitha; Chow, Nancy A et al. (2018) Genomic insights into multidrug-resistance, mating and virulence in Candida auris and related emerging species. Nat Commun 9:5346
Lebreton, François; Valentino, Michael D; Schaufler, Katharina et al. (2018) Transferable vancomycin resistance in clade B commensal-type Enterococcus faecium. J Antimicrob Chemother 73:1479-1486

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