Our research aims to understand how bacterial pathogens interact with the host using a combination of functional genomics and single gene-level functional studies. We are interested in understanding host-bacterial interactions that are key to persistent infections, with a focus on bacterial strategies to survive within the host, including intracellular survival and formation of biofilm communities. 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 recent research has also centered on understanding the role the microbiota plays in modulating host-pathogen interactions. We anticipate our research to lead to new strategies for drug and vaccine development against highly antibiotic resistant pathogens.
Major areas of interest in the group include:
Colonisation of the gut by Clostridioides difficile:
Interactions of nosocomial pathogen C. difficile with the gut epithelium and with the gut microbiota 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. One of our current interests include the development of new cell-based systems to enable pathogen-host-microbiota interactions.
C. difficile infecting human epithelial cell layers 24h and 48h after infection in an in vitro human gut infection model (C. difficile: green, nuclei: blue, actin: red)
Intracellular survival of bacterial pathogens:
Intracellular pathogens are hard to target, particularly in bone infections. Diagnosis of bone infections is also problematic, with new markers urgently needed. Current work focuses on understanding bacterial factors important for intracellular survival of Staphylococcus aureus and Mycobacterium tuberculosis and developing antimicrobials that target intracellular pathogens. In collaboration with the Perrier group in Chemistry, we are developing nanoparticle-based approaches to delivering antibiotics to effectively kill intracellular bacteria.
The role of type VII secretion systems in Staphylococcus aureus-host interactions:
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
The Unnikrishnan Lab 