Research Projects

Antimicrobial resistance (AMR) is one of the most pressing threats to global health, with Escherichia coli emerging as a prominent multidrug-resistant pathogen responsible for a wide range of infections. While conventional AMR mechanisms such as enzymatic degradation of antibiotics, target alteration, and efflux pump activity are well established, recent attention has shifted toward the structural and physiological features of bacteria that contribute to drug tolerance, particularly within biofilm communities (Mohanty et al., 2021, Almatroudi 2025). Biofilms are complex, surface-attached bacterial communities encased in a self-produced extracellular polymeric substance (EPS) that confers protection from environmental stresses, including antibiotic exposure. Among the major matrix components, functional amyloids such as curli fibers play a crucial role in establishing biofilm architecture, mediating cell-cell adhesion, and enhancing surface colonization (Siri et al., 2024). Curli fibers are encoded by the csg operon (csgA, csgB, csgD) and are actively expressed during biofilm development, particularly under nutrient-limited or stress conditions (Bhoite et al., 2019). Recent studies suggest that curli fibrils not only contribute to structural integrity but may also serve as a physical barrier, reducing the penetration of antimicrobial agents into the biofilm interior (Akbey and Andreasen, 2022). Moreover, curli expression is tightly regulated by stress-response systems and global transcriptional regulators, indicating a complex interplay between environmental sensing, amyloid production, and adaptive resistance (Khambhati et al., 2021, Yan et al., 2023). Despite their significance, the role of curli amyloids in mediating AMR in E. coli remains poorly understood and largely unexplored at the molecular level. This project aims to decipher the involvement of curli-mediated amyloid formation in the antimicrobial resistance of E. coli, with an emphasis on biofilm-related resilience. The study will include the evaluation of curli production under antibiotic stress, expression profiling of csg genes at different biofilm stages, and the development of curli-deficient mutants to assess their impact on antibiotic susceptibility and biofilm architecture. Through this integrated approach, the study seeks to provide a comprehensive understanding of how functional amyloids contribute to AMR in E. coli. The findings may uncover novel regulatory nodes and structural features that can be targeted to enhance antibiotic effectiveness. By bridging structural biology, gene regulation, and antimicrobial research, this work holds potential for developing new strategies to combat persistent and drug-resistant bacterial infections.