Ghady Haidar, MD, has been awarded funding in the amount of $895,725 for a five-year K23 Mentored Patient-Oriented Research Career Development Award from the National Institutes of Health/National Institute of Allergy and Infectious Diseases (NIH/NIAID) entitled “The Gut Microbiome in Carbapenem-Resistant Enterobacteriaceae (CRE) Colonization, Persistence, Infection, and Tolerance after Lung or Liver Transplantation.” The K23 program “support(s) the career development of individuals with a clinical doctoral degree, who have the potential to develop into productive, clinical investigators, and who have made a commitment to focus their research endeavors on patient-oriented research.” Dr. Haidar will be mentored by Drs. Cornelius J. Clancy, MD; Alison Morris, MD, MS; M. Hong Nguyen, MD; Barbara Methe, PhD; and, Maria Brooks, PhD.
Dr. Haidar will study the genetic characteristics of CRE that cause gut colonization, persistence, and infection after lung/liver transplant, the phenomenon of tolerance in CRE, and the gut microbiota environment associated with these events. His preliminary data suggest that (1) lung/liver transplant recipients are at high risk for CRE colonization, with a subset developing persistent CRE colonization and recurrent infections months to years after transplant, (2) last resort antibiotics like ceftazidime-avibactam can induce tolerance in CRE in vitro, and (3) rectal CRE colonization after lung/liver transplant is associated with marked gut dysbiosis and predominance of Proteobacteria. The scientific premise of this study is that long-term CRE colonization after lung/liver transplant is a result of persistence of antibiotic-tolerant CRE isolates that colonize the gut early after transplant, a process that is associated with a reduction in stool diversity and abundance of Proteobacteria and maintained by ongoing dysbiosis. This project will provide novel insights into the genomic epidemiology and gut microbiome of lung/liver transplant recipients through the entire spectrum of CRE colonization and disease.
Dr. Haidar will longitudinally characterize serial CRE isolates from patients and study the gut microbiome environment in which CRE colonization, persistence, and infection occur, which will lead to future studies evaluating the mechanisms of tolerance among CRE isolates after transplant, and of strategies to modify the microbiome of transplant recipients with CRE infections. Dr. Haidar’s project will advance our understanding of pathogen and host-specific mechanisms of CRE colonization and infection after solid organ transplant (SOT). His findings will inform the rational design of trials of strategies to manipulate the microbiome to prevent CRE colonization from occurring, or to eradicate established colonization and treat CRE infection. These data will also lead to studies of the mechanistic basis of tolerance and resistance.