Life Sciences & Biotechnology
Title : | CRISPR-Cas systems in Acinetobacter baumannii: role in bacterial fitness, antibiotic resistance and implications for antibacterial therapy |
Area of research : | Life Sciences & Biotechnology |
Focus area : | Microbiology, Molecular Biology |
Principal Investigator : | Dr. Ruchi Singh, ICMR-National Institute of Pathology, Delhi |
Timeline Start Year : | 2023 |
Timeline End Year : | 2026 |
Contact info : | ruchisp@gmail.com |
Details
Executive Summary : | Due to the worldwide occurrence of drug-resistant Acinetobacter baumannii and its ability to rapidly develop resistance against all classes of antibiotics, World Health Organization has classified this pathogen as a critical priority pathogen for developing novel antibiotics/ therapy. Several alternative treatment strategies, including phage-based therapies, are being explored to complement the existing and novel antibiotics. Despite the high possibilities of clinical success in A. baumannii and other MDR bacterium, the evolution of bacterial resistance to phages is a primary concern about phage-based therapies. CRISPR-Cas systems have been shown to be vital for genome editing and affect bacterial virulence and antibiotic resistance; however, the role of CRISPR-Cas systems in regulating antibiotic resistance in A. baumannii is not known. Strong antibiotic selection pressure may lead to loss or inactivation of the CRISPR-Cas system in the bacterial population. This trade-off between the CRISPR-Cas system and resistance determinants can be explored to design novel treatment strategies. About 15 per cent of the A. baumannii isolates harbour either type I-F1, type I-F2 or the co-existence of type I-F1 and I-F2 CRISPR- cas systems. We hypothesize that the co-existence of the two CRISPR Cas systems may be more efficient in limiting phage entry, and phage-based therapy may not be effective on these isolates. We will investigate the role of different CRISPR Cas systems found in A. baumannii in drug resistance by comparative genotypic and phenotypic characters, genome and transcriptome analysis of paired sensitive and resistant (lab generated after exposure to colistin) isolate carrying different CRISPR- cas systems. The experimental evidence for the role of these systems and their impact on the treatment will be generated, which can help scientists and policymakers devise strategies to combat the resistant infection using novel phage-based therapies. We will establish a library of a broad range of A. baumannii-specific bacteriophages that can serve the nearest possibilities of phage therapies in India. Through this study, we will also develop a tool for CRISPR-Cas typing in A. baumannii that can form the basis for personalized therapeutic approaches and precision medicine. This CRISPR Cas typing tool can be used for molecular profiling of infective A. baumannii in the patient, and the treating physician will be able to optimize the efficiency or therapeutic benefits of antibiotic or phage-based therapy for particular groups of patients. |
Total Budget (INR): | 42,76,152 |
Organizations involved