Antibiotic resistance of bacteria poses an immediate threat to human health. Infections due to multidrug resistant (MDR) “superbugs” are difficult to eradicate, they are associated with morbidity and mortality, and are an expanding economic burden. As a team of molecular microbiologists, our overarching objectives are (i) to understand precisely how bacteria evolve to overcome the clinician’s arsenal of therapeutics and (ii) to critically assess new treatment paradigms. One alternative strategy our research group is currently focused on is the application of bacterial viruses known as phage therapy (PT).
We apply a bedside-bench-bedside approach for the study of infectious diseases. We collect and analyse bacteria from patients over the course of infection, generating longitudinal strain pairs/series. In a reverse translational framework, we try to understand why treatments are failing at the genetic level. Using Staphylococcus aureus and Pseudomonas aeruginosa as model opportunistic pathogens, we perform comparative genomics using short and long read sequencing approaches, genome-wide mutagenesis screening (Tn-Seq), transcriptomics (RNA-seq), and targeted mutagenesis (engineered single nucleotide polymorphisms [SNP], gene deletions, and in trans complementation) to define novel mechanisms of antibiotic resistance, and the formation of antibiotic-tolerant subpopulations called ‘persisters’.
In the context of PT, we are focused on finding new phages that may be suitable for therapy, applying phages in infection setting specific experimental models, and understanding phage therapeutic failures in human clinical trials.