Texas Children’s, Baylor College and other area institutions receive $12 million NIH grant to study multidrug resistance
HOUSTON – (Oct. 2, 2020) – The National Institute of Allergy and Infectious Diseases (NIAID) awarded a five-year, $12 million grant to the Dynamics of Colonization and Infection by Multidrug-Resistant Pathogens in Immunocompromised and Critically Ill Patients (DYNAMITE) program, which includes researchers from the Microbiome Center at Texas Children’s Hospital and Baylor College of Medicine, as well as several other institutions in the Texas Medical Center, to study factors that increase the risk of multidrug-resistant bacterial infections in severely ill and immunocompromised patients.
DYNAMITE is a multi-institutional project with contributions from the Microbiome Center at Texas Children’s and Baylor College, the Center for Antimicrobial Resistance and Microbial Genomics (CARMiG) at McGovern Medical School, the Center for Infectious Diseases at the UTHealth School of Public Health, The University of Texas MD Anderson Cancer Center, The University of Houston, Rice University, and the Gulf Coast Consortia.
Multidrug-resistance is an emerging public health concern that is classified as a pressing priority by the United Nations. Many critically-ill and immunocompromised patients, like cancer or transplant patients, are at a greater risk for infections by gut multidrug-resistant (MDR) bacteria, such as vancomycin-resistant enterococci (VRE), extended spectrum β-lactamase producing/carbapenem-resistant Enterobacteriaceae (ESBL-E/CRE) and Clostridiodes difficile. However, the underlying pathological reason for their increased susceptibility has remained a mystery. Moreover, it remains unclear why only some of these patients are susceptible to MDR infections while others with similar preexisting conditions are not affected.
With this federal funding, researchers in the DYNAMITE program propose to address these critical questions by dissecting the interrelationships between an individual’s gut microbiota, their clinical status, the antimicrobial resistance and other host factors to establish how they contribute to the growth and infection by the above-mentioned three groups of MDR bacteria.
The study will be conducted with 500 adult patients admitted to the intensive care units (ICU) at Memorial Hermann Hospital-Texas Medical Center and with 500 adult patients undergoing stem cell transplants at MD Anderson Cancer Center. The study will combine the state-of-the-art clinical and epidemiological analyses using cutting-edge “omics” technologies, including whole genome sequencing, meta-genomics sequencing, proteomics and metabolomics. Successful completion of this project will not only further knowledge of how an individual’s gut microbiome and their immune status determines their susceptibility to recalcitrant bacterial infections, but will also help researchers understand and develop novel strategies and tools for the prevention, prediction, diagnosis and treatment of gut-derived MDR infections – a growing medical issue for which no therapeutic options exist currently.
“One of the major driving forces behind this proposal, which was also instrumental in us getting this funding, is the unique patented technology that was developed as a part of a previous NIAID U01 systems biology grant awarded to Texas Children’s Microbiome Center and is currently being licensed to pharmaceutical companies. The innovative technology developed by Drs. Qinglong Wu and Tor Savidge, helps us to accurately predict the disease susceptibility of each patient to facilitate personalized infectious disease management. Over the years, Texas Children’s has invested millions of dollars to develop a state-of-the-art mass spectrometric capability, which is now paying dividends in identifying clinical biomarkers of infectious disease susceptibility under the leadership of the DYNAMITE co-director Dr. Anthony Haag,” Dr. Tor Savidge, associate director of Texas Children’s Microbiome Center and associate professor of Pathology and Immunology at Baylor College, said.
Cesar A. Arias, MD, PhD, professor and director of CARMiG at McGovern Medical School and director of The Center for Infectious Disease at UTHealth School of Public Health, will serve as co-principal investigator (PI) and communicating PI of DYNAMITE. Sam Shelburne MD, PhD, (MD Anderson Cancer Center); and Tor Savidge PhD, (Texas Children Hospital and Baylor College of Medicine); are co-principal investigators of the program.
Additional co-investigators include Anthony Haag and Qinglong Wu (Texas Children’s), Alton Swennes (Baylor College) Blake Hanson (UTHealth School of Public Health); Kevin Garey (University of Houston), Todd Treangen (Rice University); and Suzanne Tomlinson (Gulf Coast Consortia and Rice University).