Centre for Cellular and Molecular Biology, Uppal Road, Hyderabad, India
Role of host membrane cholesterol in pathogen entry: A tale of two pathogens
Diseases caused by intracellular pathogens represent a major public health problem worldwide. The host plasma membrane offers the first portal for an intracellular pathogen to establish infection within a cell. The process of entry involves several receptors on the plasma membrane of the host cell, which are intimately associated with the surrounding membrane microenvironment. As a consequence, the role of membrane lipids in the entry of intracellular pathogens assumes significance. In this talk, I will highlight the role of host membrane cholesterol in regulating the entry of intracellular pathogens such as Leishmania and Mycobacterium. Our results show that pathogen entry is inhibited upon depletion as well as complexation of membrane cholesterol. Interestingly, our results show that an optimum level of host membrane cholesterol is necessary for efficient infection by pathogens. We propose a general mechanism, based on cholesterol-induced conformational changes, involving cholesterol binding sites in host cell surface receptors that are implicated in pathogen entry. A therapeutic strategy targeting modulation of membrane cholesterol has the advantage of avoiding the commonly encountered problem of drug resistance in tackling infection by intracellular pathogens. We envision that insights into the role of host membrane cholesterol in pathogen entry would be instrumental in the development of novel therapeutic strategies to effectively tackle intracellular pathogenesis.
1. Pucadyil, T.J., Tewary, P., Madhubala, R., and Chattopadhyay, A. (2004) Mol. Biochem. Parasitol. 133: 145-152.
2. Pucadyil, T.J., and Chattopadhyay, A. (2007) Trends Parasitol. 23: 49-53
3. Kumar, G.A., Roy, S., Jafurulla, M., Mandal, C., and Chattopadhyay, A. (2016) Biochim. Biophys. Acta (Biomembranes) 1858: 2088-2096
4. Viswanathan, G., Jafurulla, M., Kumar, G.A., Raghunand, T.R., and Chattopadhyay, A. (2015) Chem. Phys. Lipids 189: 19-27
5. Kumar, G.A., Jafurulla, M., and Chattopadhyay, A. (2016) Chem. Phys. Lipids 199: 179-185
Contact: Evert Haanappel (email@example.com)
Note for visitors: Please come with a valid identity card
13:30 - 14:30
Seminar room - IPBS - Campus 205