This K24 renewal application provides 33% salary effort for Dr. Hauser and supplements institutional support for his continued mentoring of MD and MD/PhD fellows and junior faculty and for expansion of his patient- oriented research program. A focus of the Hauser Lab is to identify biomarkers of Pseudomonas aeruginosa that define particularly aggressive strains. Past work has successfully identified several genes that are associated with more severe infections in mouse models. The goal of the proposed research is to expand these studies into populations of human patients. In the first project, the focus will be on acute respiratory infections. P. aeruginosa genes associated with strains that cause especially severe ventilator-associated pneumonia in intensive care unit patients will be identified. To begin to parse genes into functional categories, those genes that allow P. aeruginosa to resist killing by neutrophils will also be identified. In the second project, the focus will be on chronic respiratory infections. A systems biology approach will be used to identify P. aeruginosa strains capable of persisting in the airways of individuals with cystic fibrosis. A mouse model of chronic airway infection will then be used to determine whether aspects of these strains play a causal role in persistence. These projects combine powerful genomic, genetic, and microbiological techniques with human specimens and corresponding clinical data to yield cutting-edge patient-oriented research. They are thus ideal training vehicles for junior clinician investigators and have the potential to lead to improvements in patient care. Mentees will participate in a rigorous and broad mentoring program that utilizes the many resources available at Northwestern University to maximize their development into independent patient-oriented researchers. In summary, this K24 award will provide salary support and research funds to allow Dr. Hauser to spend a substantial portion of his effort mentoring clinical fellows and junior faculty in patient-oriented research and to expand his patient-oriented research program.

Public Health Relevance

This K24 renewal award provides salary support for Dr. Hauser to spend 33% of his time mentoring MD fellows and junior faculty and expanding his patient-oriented research program. Patient-oriented research will focus on the bacterial pathogen Pseudomonas aeruginosa and will provide an ideal vehicle for the training of junior clinician investigators.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Midcareer Investigator Award in Patient-Oriented Research (K24)
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Microbiology and Infectious Diseases B Subcommittee (MID)
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Ernst, Nancy L
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Northwestern University at Chicago
Schools of Medicine
United States
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Rutherford, Victoria; Yom, Kelly; Ozer, Egon A et al. (2018) Environmental reservoirs for exoS+ and exoU+ strains of Pseudomonas aeruginosa. Environ Microbiol Rep 10:485-492
Kociolek, Larry K; Ozer, Egon A; Gerding, Dale N et al. (2018) Whole-genome analysis reveals the evolution and transmission of an MDR DH/NAP11/106 Clostridium difficile clone in a paediatric hospital. J Antimicrob Chemother 73:1222-1229
Krapp, Fiorella; Ozer, Egon A; Qi, Chao et al. (2018) Case Report of an Extensively Drug-Resistant Klebsiella pneumoniae Infection With Genomic Characterization of the Strain and Review of Similar Cases in the United States. Open Forum Infect Dis 5:ofy074
Hughes, A J; Knoten, C A; Morris, A R et al. (2018) ASC acts in a caspase-1-independent manner to worsen acute pneumonia caused by Pseudomonas aeruginosa. J Med Microbiol 67:1168-1180
Rhodes, Nathaniel J; Cruce, Caroline E; O'Donnell, J Nicholas et al. (2018) Resistance Trends and Treatment Options in Gram-Negative Ventilator-Associated Pneumonia. Curr Infect Dis Rep 20:3
Prickett, Michelle H; Hauser, Alan R; McColley, Susanna A et al. (2017) Aminoglycoside resistance of Pseudomonas aeruginosa in cystic fibrosis results from convergent evolution in the mexZ gene. Thorax 72:40-47
Henry, Christopher S; Rotman, Ella; Lathem, Wyndham W et al. (2017) Generation and Validation of the iKp1289 Metabolic Model for Klebsiella pneumoniae KPPR1. J Infect Dis 215:S37-S43
Krapp, Fiorella; Morris, Andrew R; Ozer, Egon A et al. (2017) Virulence Characteristics of Carbapenem-Resistant Klebsiella pneumoniae Strains from Patients with Necrotizing Skin and Soft Tissue Infections. Sci Rep 7:13533
Ozer, Egon A; Hauser, Alan R; Gerding, Dale N et al. (2017) Complete Genome Sequence of Clostridioides difficile Epidemic Strain DH/NAP11/106/ST-42, Isolated from Stool from a Pediatric Patient with Diarrhea. Genome Announc 5:
Hauser, Alan R; Mecsas, Joan; Moir, Donald T (2016) Beyond Antibiotics: New Therapeutic Approaches for Bacterial Infections. Clin Infect Dis 63:89-95

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