Jyothi Rengarajan, PhD
Infectious Diseases and Emory Vaccine Center
Yerkes National Primate Center
Adjunct Assistant Professor
Department of Microbiology and Immunology
Phone: 404 727 8174
Tuberculosis (TB), caused by the bacterium Mycobacterium tuberculosis (Mtb), is a highly contagious airborne infectious disease that affects about 9 million people worldwide, causing up to 2 million deaths each year. The current 6-9 month standard regimen of chemotherapy for tuberculosis (TB) involves multiple antibiotics and is long and arduous. The main reason for the long duration of anti-TB treatment is that although antibiotics effectively decrease Mtb load during the first 2 months of treatment, bacteria are not eradicated from the host during this time. Rather, Mtb continues to persist at low levels within tissue and requires a minimum of 4 additional months of treatment to achieve cure. Relapse of infection can occur if treatment does not result in sterilization. Moreover, difficulties in adhering to treatment regimens have contributed to increased rates of multi- and extensively drug-resistant TB (MDR- and XDR-TB) globally. These challenges point to an urgent need for shorter, more efficacious treatment regimens. In addition, there is a critical need for better treatment-monitoring tools to effectively detect a patient’s response to treatment against drug-susceptible and drug-resistant Mtb strains. We are interested in identifying new targets for improving current anti-TB treatment regimens as well as biomarkers of treatment response that will aid in developing better tests for monitoring anti-TB treatment.
We hypothesize that detrimental immune responses and lung pathology induced by Mtb interfere with optimal antibiotic-mediated killing of Mtb, particularly within granulomatous lesions in the lung, which serve as reservoirs of viable bacteria and prevent optimal drug penetration. Thus immune therapies that tip the balance away from pathogenic immunity and towards beneficial immunity have the potential to accelerate the sterilizing activity of antibiotics and shorten treatment duration. We have identified cell-wall associated and secreted Mtb proteins that modulate innate and adaptive immune responses. We are delineating the underlying molecular and biochemical mechanisms and developing inhibitors against these proteins with a view towards designing new drugs and immune-therapeutic targets for TB that could synergize with antibiotics to improve and/or shorten treatment. We will test candidate small molecule inhibitors in mouse models and eventually in nonhuman primates. In addition, through collaborative patient-based studies, we have identified host biomarkers that correlate with treatment response in individuals undergoing anti-TB treatment and are engaged in translational studies to validate these observations within ongoing clinical treatment trials for TB and to explore the potential of developing diagnostic and treatment-monitoring tools for TB.
- View publications on PubMed