Components of c-di-GMP and MSN signalling pathways in bacteria. At the cellular level, the concentration of c-di-GMP and ppGpp is determined by the action of diguanylate cyclases (DGC) and Rel enzymes, respectively. Through the interaction with different receptors c-di-GMP and ppGpp modulates cell motility and traits associated with bacterial
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Our Research Focus
Deciphering the molecular mechanisms of signaling in bacteria
Our lab is situated in the Department of Biological Sciences and Bio-Engineering (BSBE) at IIT Dharwad. Here at BSBE, our research is primarily focused on molecular understanding of how bacterial pathogens sense, adapt, and survive in hostile environments, the knowledge that is urgently needed in the era of antimicrobial resistance (AMR). Bacterial infections remain a major global health challenge, intensified by the rapid emergence of AMR. In the wake of the COVID-19 pandemic, the World Health Organization (WHO) has highlighted the critical priority posed by infections caused by ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species). These organisms combine high transmissibility with formidable antibiotic resistance, underscoring the pressing need for innovative therapeutic strategies beyond conventional antibiotics.
Our research deciphers the molecular and structural basis of bacterial signaling networks, with particular emphasis on second messengers such as c-di-GMP, (p)ppGpp, and c-di-AMP. These molecules act as master regulators of biofilm formation, stress responses, virulence, persistence, and cell cycle control in major pathogens, including ESKAPE organisms.
We employ an integrated structural biology approach, combining X-ray crystallography and cryo-electron microscopy (Cryo-EM) with mass spectrometry–based proteomics, biochemical and biophysical assays, molecular docking and molecular dynamics simulations to reveal how signaling proteins function at atomic resolution. Our previous work has uncovered novel second-messenger effector proteins, new mechanisms of bacterial cell cycle regulation, and direct cross-talk between global signaling pathways.
We are anticipating targeting bacterial survival and adaptation pathways rather than viability alone, our lab aims to identify non-traditional drug targets and contribute to the development of next-generation antimicrobial strategies.
Our current and future research aims to identify new therapeutic targets and uncover their molecular mechanisms to selectively disrupt bacterial pathways involved in stress response, antibiotic resistance, persister formation, quorum sensing, and biofilm formation.
Our approach focuses on precisely targeting pathogenic bacteria, particularly ESKAPE pathogens, while preserving beneficial gut microbial communities. This selectivity distinguishes our strategy from conventional antibiotics, which often act indiscriminately and disrupt the microbiome. We believe that insights from this work will enable the development of next-generation antibiotics and novel synergistic therapeutic combinations, contributing meaningfully to the fight against antimicrobial resistance (AMR).
Funding
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