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Meera Unnikrishnan

Technical Summary

Our group is interested in understanding how bacterial pathogens interact with host cells using a combination of whole genome-based strategies and single gene-level functional studies.

p62 wildtypeBacteria have developed several strategies to survive within the host, including intracellular survival and formation of biofilm communities, enabling them to escape antibiotics and immune responses. Investigating such mechanisms, both from the bacterial and host standpoints, is crucial for the development of effective preventive and therapeutic approaches, particularly for recurrent bacterial infections. Our research focuses on understanding host-bacterial interactions that are key to persistent infections.

Major areas of interest in the group include:

Colonisation of the gut by Clostridium difficile: Interactions of nosocomial pathogen C. difficile with the gut epithelium are poorly understood. The roles of many extracellular and surface proteins of C. difficile in colonisation and establishment of infection remain unclear. We have previously identified bacterial factors, including secreted proteins that may play important roles during gut infection. Additionally, we have characterized processes such as C. difficile biofilm formation and proteins that modulate bacterial community formation in vitro. Current work in the group focuses on understanding bacterial mechanisms underlying C. difficile colonisation and persistence. We are also developing novel cell-based systems to enable host-C. difficile interaction studies during infection.

Type VII (Esx) secretion systems of Staphylococcus aureus: The intriguing staphylococcal type VII secretion systems secrete virulence factors that have excellent vaccine and drug potential. However, their functions are during infection are not clear. Our previous work has shown a role for the staphylococcal Esx proteins in modulating intracellular infection. We are currently examining how these specialized systems mediate interactions with host cells and modulate immune responses. In addition, we are interested in understanding bacterial factors important for intracellular survival of S. aureus and their role in chronic infections and antimicrobial resistance.

Selected publications:

1. Korea, C.G., Balsamo, G., Pezzicoli, A., Merakou, C., Tavarini, S., Bagnoli, F., Serruto, D.,and Unnikrishnan, M. (2014) Staphylococcal Esx proteins modulate apoptosis and release of intracellular Staphylococcus aureus during Infection in epithelial cells. Infect. Immun. 82(10): 4144-53

2. Cafardi, V., Biagini, M., Martinelli M., Leuzzi R., Rubino J.T., Cantini F., Norais, N.,Scarselli M., Serruto, D. and Unnikrishnan M (2013) Identification of a novel zinc metalloprotease through a global analysis of Clostridium difficile extracellularproteins. PLoS ONE 8(11): e81306

3. Dapa, T., Leuzzi, R., Ng, Y.K., Baban, S., Kuehne, S., Scarselli, M., Minton, N.P., Serruto,D., Unnikrishnan, M. (2013) Multiple factors modulate biofilm formation by the anaerobic pathogen Clostridium difficile. J. Bacteriol. 195(3): 545-55

4. Siegrist, M.S.*, Unnikrishnan, M.* McConnell, M.J., Borowsky, M., Cheng, T.Y., Siddiqi, N., Fortune, S.M., Moody, D.B., Rubin, E.J. (2009) Mycobacterial Esx-3 is required for mycobactin-mediated iron acquisition. Proc Natl Acad Sci U S A. 106(44): 18792-7