Surface proteins and proteinaceous filaments are used by gram-positive bacteria to colonize or invade human tissues. Structural view of these adhesive proteins and protein complexes at the atomic level and knowledge about their assembly and anchoring will enable us to invent strategies to prevent their attachment and thus block infection.
Our lab focuses on both the assembly of surface adhesins and the enzymes involved in their assembly and anchoring. Till now, we provided the first perceptive of the gram-positive bacterial surface protein assembly and adhesive mechanism. We also provided glimpses of the catalytic machinery of a highly conserved enzyme responsible for anchoring these surface proteins. We are presently focusing our efforts to understand the assembly of proteinaceous filaments called fimbriae or pili and the enzymes essential for their assembly. Further understanding of this assembly will help us identify the inhibitors that can block the microbial attachment and such inhibitors can be considered as a new class of antibiotics that do not promote microbial resistance.
The human complement system contributes to host defense against bacterial infections directly by its opsonic, inflammatory and lytic activities and indirectly enhancing antibody responses. Gram-negative bacteria are susceptible to lysis by the complement whereas it plays an opsonic role in clearing Gram-positive bacteria. Various deceases are linked to defective, deficient and inappropriately activated complement and unsurprisingly, pathogens have developed invasive components that mimic complement proteins to escape detection and also in creating defective compliment.
Activation is essential for the expression of complement biological activity and understanding the activation is vital for attempting its pharmacological control. The generation of the truncated third complement component (C3b) is the focal point of complement function, indeed the deposition of C3b on the surface of invasive microorganism is the most important result of complement activation. Our lab is primarily focused on exploring and exposing the structural correlates of enzymes factor D, factor B and C2 that play critical role in generating C3b. As C3b, C4b and C3-convertases C3b.Bb and C4b.C2a, the enzymes that are essential for the generation of C3b whose catalytic apparatus are provided by factor B and C2, are the pivotal components of human complement, our ultimate goal is to expose the assembly and the structural correlates of C3-convertases. Such structural knowledge would be the stepping stone for complement inhibition and modulation.