Author: Todd Pryce
Pryce, Todd, 2025 Molecular Diagnostic Approaches Responding to New Challenges in Clinical Microbiology , Flinders University, College of Medicine and Public Health
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Over the past few decades, advances in microscopy instrumentation, laboratory automation for culture and susceptibility testing, and rapid organism identification using matrix-assisted laser desorption ionization-time of flight mass spectrometry have dramatically changed clinical microbiology. Molecular methods, which have rapidly evolved alongside these technologies, continue to address many longstanding challenges in microbiology—most notably the time delays for culture and subsequent pathogen identification. The development of the Polymerase Chain Reaction (PCR) technique transformed clinical microbiology, and I was fortunate to be among its early practitioners. As such, rapid pathogen detection and subsequent identification using PCR have been at the core of diagnostic molecular microbiology since its inception. Over time, a wide array of PCR assays have been applied to detect, identify and quantify many microbial pathogens. As exampled by my work in this thesis, PCR has been applied to many sub-disciplines in microbiology due to the speed of the application its high sensitivity and specificity. Today, PCR methodology continues to assist clinicians in identifying infections, promptly administering tailored therapies, and measuring the efficacy of treatment. Consequently, PCR methodologies have reduced morbidity and mortality, length of hospitalisation, inform appropriate administration of antimicrobial agents, which in turn minimises the development of antimicrobial resistance and promotes antimicrobial stewardship.
This thesis details my body of work through twelve prior publications, identifying the problems and challenges with traditional methods of diagnosis and pathogen identification in a clinical laboratory setting, and addressing these issues with contemporary molecular methodology. The publications presented in the thesis contributes to the scientific knowledgebase of molecular test development and applications in this field. The methods and concepts presented in this thesis have been developed over 30 years of experience, alongside continuous advancements in molecular techniques. Together, they contribute to a comprehensive understanding and establish a precedent for how PCR can be applied to overcome complex challenges and anticipate future problems. Here, I address three major on-going laboratory and clinical challenges: (a) the detection and identification of fungal pathogens in the context of rapid identification, cross reactivity with human DNA, and challenging biological specimens, b) improving the sensitivity and specificity of Neisseria gonorrhoeae testing, particularly for pharyngeal infections, whilst progressively addressing the growing rate and threat of antimicrobial resistance (AMR), via early AMR detection and individualised therapy, and c) COVID-19 pandemic, through developing novel approaches to sample preparation, testing throughput and standardisation in the context of a new pathogen, limited resources and time critical responses.
Keywords: Molecular, Diagnostics, Challenges, Microbiology
Subject: Microbiology & Infectious Diseases thesis
Thesis type: Doctor of Philosophy
Completed: 2025
School: College of Medicine and Public Health
Supervisor: Professor Jillian Carr