Title: Investigating pneumococcal adaptation to intracellular survival within the host and characterization of macrophage extracellular vesicles for novel vaccine development.
Department of Biotechnology [DBT]
The respiratory pathogen, Streptococcus pneumonia colonizes the upper respiratory tract and is a major cause of life-threatening diseases such as pneumonia, septicaemia and meningitis, resulting in death of over 800,000 children annually. Pneumococci have several virulence factors such as the polysaccharide capsule, pore-forming toxins to evade the host immune response and establish disease. The main goal of our lab is to investigate mechanisms underlying pneumococcal intracellular survival within host cells and bacterial reprogramming of immune cells. Using a combination of flow sorting, RNA sequencing, Luminex, mass-spectrometry we will investigate the bacterial and host factors that promote bacterial survival within the host.
In addition, we will investigate the molecular composition and immunomodulatory role of extracellular vesicles from pneumococci- infected macrophages and explore their potential for immunotherapies.
We recently discovered that pneumococcal bacteria can also survive intracellularly within dendritic cells and lung alveolar macrophages pneumococci by avoiding fusion with the bactericidal lysosomes and remain viable with the macrophages. In this manner, the macrophages serve as a "silent" persistent reservoir for the bacteria to reestablish colonization and thereby transmit itself to new hosts. Our lab is interested to study the mechanisms that promote bacterial survival within host cells and immunophenotype macrophages that are permissive to bacterial survival.
Although pneumococci are commensal bacteria colonizing the nasophayrnx, under certain conditions they can migrate to the lungs and other organs such as ear, brain, heart to cause invasive diseases. Our lab is interested to study the mechanisms underlying how the bacterial adapt to the different niches and understand why colonization does not confer immunity against re-infection.
Current Research Grants
Disarming bacterial pathogens using novel peptides that target pore-forming toxins: from in silico to in vivo
Department of Science & Technology [DST]
Unravelling bacterial immunoevasion and host immune reprogramming strategies in invasive pneumococcal diseases.
DST-SERB Start-up Grant [SRG]
Previous/ Completed Research Grants
Developing novel host-derived peptides to neutralize bacterial pore-forming toxins in bacteremic patients
Karolinska Institutet, Stockholm, Sweden 2018-2020