Nanotechnology-based diagnostic for rapid detection of bacterial infection in biological fluids to monitor antibiotic resistance and reduce hospital acquired infections

The rise in global burden of infectious diseases accompanied with the significant rise in antibiotic resistance world-wide and here in Qatar prompt immediate action to combat the emerging threat of antibiotic resistance in bacteria. Based on the latest report on the global burden of antibiotic resistance, the World Health Organization declared that antibiotic resistance is the biggest global threat to public health. Antibiotic resistance is accelerated by the misuse of antibiotics in human and livestock animals. This problem is present in all countries and affects all ages of people. Specifically, antibiotic resistance problem raises significant concern in hospitals due to hospital-acquired infection where it is associated with increased mortality and longer hospital stay at a considerable health and financial burden. Similarly, the spread and the increase in antibiotic resistance in community-acquired infections is also very alarming and imposes the threat of untreatable bacterial infection. The current gold standard approach to detect bacterial infections in clinical samples (biological fluids) requires three days of bacterial culture to obtain the diagnosis and antibiotic sensitivity results. This approach, although very accurate results in considerable delay in initiating proper treatment which increase the transmission of infection mainly hospital-acquired infections. Therefore, rapid detection of infection would lead to rapid clinical interventions, which mitigate the spread of infection and support antibiotic stewardship consequently reducing the burden of hospital-acquired infections. The goal of this proposal is to develop a highly innovative sensor for rapid detection of bacterial infections in biological fluids. The proposed biosensor is a culture-free diagnostic method utilizing nanotechnology-based fabricated silver nanorods array (AgNR) as a substrate for the Surface Enhanced Raman Spectroscopy (SERS). We already reported the proof-of-concept study using this novel SERS-based diagnostic where we showed that rapid detection of Pseudomonas aeruginosa biomarkers in sputum and exhaled breathe condensates (EBC) from patients with cystic fibrosis. This project will focus on identifying unique biomarkers SERS spectra of antibiotic resistant bacteria. This method is highly sensitive, fast, cheap, and can be implemented at bedside using portable (hand-held) Raman spectroscope. The following strains are causing the majority of infections that are usually isolated at Hamad Clinical and Diagnostic Microbiology laboratory: E. coli, Pseudomonas aeruginosa, Klebsiella, Staphylococcus aureus (MRSA); Acinetobatcer baumanii; Enterococci, and Enterobacter species, will be used in the discovery phase of this project. The proposed project key goal is to develop a nanotechnology-based biosensor, a point-of-care (POC) device for rapid detection of bacterial infections and early detection of antibiotic resistant bacterial pathogens which will support antibiotic stewardship, and reduce the burden of nosocomial disease and the emerging threat of antibiotic resistance. The project will have three phases of discovery, development and validation; phase one is optimization of silver nanorods arrays fabrication at University of Georgia, USA and identification of bacterial biomarkers unique SERS spectra at Qatar University; phase 2 involves integrating machine learning data analysis algorithm at Qatar Computing Research Institute to facilitate rapid bacterial detection in biological fluids obtained from Qatar Biobank at QU; phase three is translational research to validate the innovative POC use at bedside in Hamad Medical Corporation. Therefore we propose 5 Work Packages to accomplish the tasks. The first phase of the project is described in WP1 and WP2. The second phase is described in WP3 and WP4. The third phase is described WP5. The proposed Work Packages are: WP1: SERS silver nanorods array fabrication WP2: Bacterial biomarkers unique SERS identification WP3: Machine learning (AI) enabled data analysis to create central SERS library WP4: Validation of bacterial biomarkers SERS in biological fluid obtained from Qatar Biobank WP5: Validation of the novel POC accuracy in rapid detection of bacterial infections at bedside in HMC. This novel project is highly interdisciplinary owed to the collective knowledge and depth of expertise of the team that include nanotechnology physicist, biomedical scientists, clinical microbiologists, machine learning & data scientist, intensivist and infectious diseases specialist. The expertise spans from basic science to translational and clinical applied research. The research team members are hosted at five different institutions: Qatar University, University of Georgia in USA, Qatar Computing Research Institute, Qatar Biobank and Hamad Medical Corporations. The outcome of this project is to establish a powerful, high sensitivity, high specificity, fast speed, and low cost novel detection method to rapidly diagnose causative agents based on the combination of nanotechnology and host-pathogen interaction expertise. Therefore, rapid detection of bacterial infections not only would save lives but certainly have an economic impact on healthcare expenditure and enhance quality of healthcare delivery in hospitals across Qatar.

Qatar University