
In human lungs, macrophages are key defenders against bacterial infections. They ingest invading bacteria, and phagosomes containing these bacteria fuse with lysosomes to form phagolysosomes, where the bacteria are killed. However, certain pathogens, such as Mycobacterium tuberculosis (Mtb), Legionella pneumophila and Listeria monocytogenes, escape killing in phagolysosomes. Although antibiotics are available to target these pathogens, the rise of multidrug-resistant strains has further complicated treatment efforts. A key factor in the development of drug resistance is bacteria’s ability to tolerate a range of stresses, which is essential for their survival under conditions of stress, whether from host cell defenses or antibiotic treatment.
My lab investigates how polyphosphate (polyP), a phosphate polymer secreted by Mtb and other pathogens, prevents their killing in human macrophages, as well as protects bacteria from antibiotics. In a first line of research, we study how bacterial polyP modulates macrophage functions, including phagosome acidification, lysosome activity, autophagy, and cell polarization, facilitating bacterial survival within phagosomes. In a second line of research, we study how secreted polyP contributes to bacterial physiological adaptation to stress, cell envelope biogenesis, and biofilm formation. By identifying and targeting components of the polyP signal transduction pathway with small molecule inhibitors, we aim to render bacteria vulnerable to complete eradication by human immune cells. Our ultimate goal is to develop innovative strategies to effectively overcome drug tolerance and combat bacterial diseases.
My lab is actively seeking motivated and hard-working undergraduates and graduate students and, in the future, postdoctoral fellows to join my team.
SEA-PHAGES Sections
Spring 2025
Term: Spring 2025
Primary Instructor: Ramesh Rijal
Additional Instructor: Ramesh Rijal
Type: In situ (phage discovery/microbiology)
Hosts used: Mycobacterium smegmatis
Number of students: 40
Meetings per week: 1
Hours per week: 2.0