Written by Haley Zubyk, PhD Candidate, Wright Lab
Infectious diseases are generally caused by pathogenic microorganisms including bacteria, parasites, or fungi that are capable of spreading between individuals.1 While antibiotics have proven to be effective at treating many of these infections, the emergence of antibiotic resistance has served as a wakeup call with respect to the way that antibiotics are used throughout the world. This includes both the overuse and misuse of these drugs. For example, it has been demonstrated that at least 50% of patients showing signs of acute upper respiratory tract infections receive antibiotic treatments although this type of illness is primarily caused by viruses.2 The prescribing of antibiotics in these cases can be attributed to the inability to differentiate between a bacterial or viral infection within the timeframe of a patient’s visit.2 Furthermore, the general use of antibiotics that occurs without knowing exactly which microorganisms are responsible for causing an illness in comparison to prescribing targeted therapies that are specific to the infecting pathogen contributes to the spread of resistance. Traditional detection methods used to identify specific bacteria include Gram-stains, bacterial culturing, and DNA-sequencing.3 While these methods have contributed to the diagnosis, treatment, and prevention of infectious diseases, they each have limitations such as being resource-intensive, time-consuming, and requiring the presence of skilled technicians to analyze results.4 These requirements are of course exasperated in developing countries where resources are limited. Thus, the rapid and accurate identification of pathogens has become imperative in treating infected individuals and protecting the viability of our current collection of antibiotics. To help combat these challenges, point-of-care testing (POCT) methods which are on-site, simple, accurate, rapid and inexpensive are currently being explored by many researchers.1
At McMaster University, POCT is currently being investigated by an interdisciplinary group of professors – Dr. Fred Capretta and Dr. John Brennan from the Department of Chemistry and Chemical Biology, Dr. Yingfu Li from the Department of Biochemistry and Biomedical Sciences, and Dr. Carlos Filipe from the Department of Chemical Engineering – in addition to their research labs. Together, this team is working to develop printable POCT diagnostics for infectious diseases with the ability to reproducibly detect specific bacterium or species with high specificity. The design is similar to a pregnancy test, wherein a sample is spotted on a test strip which then travels to a detection pad that provides a readout after ~ 30 minutes. These test strips eliminate the need for invasive tests because patient samples such as saliva, stool, and even teardrops can be used. Specific treatments are then able to be administered to the patient, thereby aiding against the development of antibiotic resistance. Furthermore, these test strips do not require any analytical equipment or highly trained individuals, making it accessible to people in resource-limited areas.
Many factors must be considered during the design of these diagnostics. To make them specific to different infectious diseases, unique detectors are identified and incorporated into the strips (i.e. DNA aptamers, enzyme targets, small molecule-based, and biomarker-based). In terms of the DNA aptamer detectors, highly specific recognition elements are used that allow for the identification of a specific bacterium or strain. Once these detectors are developed, Research Associates Monsur Ali and Julijana Milojevic from the Capretta laboratory work in the McMaster Biointerfaces Institute to assemble these strips, print them on paper using bio-inks, and use surface chemistry to translate the binding event that occurs between these detectors and their target into a visible, colorimetric signal. This is an essential step that allows the technology to be easily used by untrained individuals. Dr. Capretta and his team have also been working to optimize the parameters of the strips so as to minimize false negative or positive read-outs.
To commercialize this product, the McMaster Biomedical Engineering and Advanced Manufacturing (BEAM) project centre is currently working on a large-scale production to verify that the strips are reproducible and fool-proof outside of the laboratory setting. Ultimately, the main goal for these printable diagnostics is that they will eventually enter the clinic for the treatment of infectious diseases. There are, however, other applications for these strips including playing a part in the drug discovery process. When drugs are developed there must be companion diagnostics available to monitor the level of drug in serum to see if it is working to clear the infection and determine the right dose. Being said, these printable diagnostics show a high-potential for not only decreasing the development of antibiotic resistance, but they may also be helpful in our own research institutes such as the IIDR and DBCAD where they can be used by our trainees to find novel treatments.
- Kim, H., Chung, D.-R. & Kang, M. A new point-of-care test for the diagnosis of infectious diseases based on multiplex lateral flow immunoassays. Analyst 144, 2460–2466 (2019).
- Caliendo, A. M. et al. Better Tests, Better Care: Improved Diagnostics for Infectious Diseases. Clin. Infect. Dis. 57, S139–S170 (2013).
- Diagnosis of Infectious Disease – Infections – Merck Manuals Consumer Version. Available at: https://www.merckmanuals.com/en-ca/home/infections/diagnosis-of-infectious-disease/diagnosis-of-infectious-disease. (Accessed: 21st August 2019)
- Wang, Y., Yu, L., Kong, X. & Sun, L. Application of nanodiagnostics in point-of-care tests for infectious diseases. Int. J. Nanomedicine 12, 4789–4803 (2017).
About the Author
Haley Zubyk, PhD Candidate
Haley joined the Wright lab in May of 2016 to work on expanding the number of characterized resistance genes that make up the Antibiotic Resistance Platform (ARP). Since then, she has completed her fourth-year undergraduate thesis in the lab which involved high-throughput screening for a natural product inhibitor of the tetracycline efflux pump, TetA. For her graduate studies, Haley is now investigating the mechanistic enzymology of β-amino acid synthesis in the peptide antibiotic edeine. Haley’s favorite things outside of the lab include coffee, Game of Thrones, and junk-food.