The pathogenic amoeba, Entamoeba histolytica and Naegleria fowleri, are a class of human pathogens that causes life threatening infections such as amoebic colitis, hepatic abscess, and primary amoebic meningoencephalitis (PAM). Currently, our lab is trying to understand how host cues modulate the invasive nature of pathogenic amoeba and how it helps in tissue destruction in a complex host environment. A brief outline of some projects is given below.

Cell-to-Cell communication and tissue invasion

Entamoeba histolytica infections are common among the human population worldwide. The parasite damages the intestinal barriers, enters into the bloodstream, travels to the liver causing hepatic abscess and in rare cases brain abscess. The host tissue damage by amoebic parasite relies on effective phagocytosis and protease secretion mechanisms. A recently specialized form of phagocytosis discovered in amoebic trophozoites is known as trogocytosis (nibbling of the live host cell). Trogocytosis is evolutionarily conserved process from ancient protists to modern cells. Recent findings suggest that the trophozoite treated with lysosomal inhibitors reduces the global trogocytosis and killing of host cells. Our aim is to understand how the amoebic lysosomes co-ordinate with trogocytosis machinery to breach the barrier of host tissue and establish the cellular niche at different organs.

Unique Rab GTPases function in membrane trafficking

Transition between prokaryotes to eukaryotes might be one of the crucial events during the evolution. Eukaryotes can be found diversely as single-celled organisms called protists, and as organized systems in multicellular organisms. The membrane-trafficking system is a defining feature of eukaryotic cells. The primitive eukaryotes (Entamoeba and Giardia) lack typical cell organelles such as mitochondria, Golgi-complex etc. The unicellular ancient pathogen E. histolytica is highly motile and encodes 98 Rab GTPases that are indicative for complex membrane trafficking routes. More than 50% of the amoebic Rab GTPases are unique, which do not share similarity with other eukaryotes. Our group is trying to learn the physiological significance of these novel Rab GTPases in the membrane transport system and pathogen-specific virulence.

Funding

DST-SERB, Govt of India, New Delhi