Molecular Horizons Seminar - Dr Carola Venturini

The continuing rise of antibiotic resistance in pathogenic bacteria is the cause of a global crisis with alarming health and economic impacts. Improved antibiotic use and alternative, or adjuvant, therapies to traditional antibiotics have therefore become an immediate priority for health agencies worldwide. In the past decade, I have been actively investigating both strategies by studying collateral effects of antibiotic use in critical care and by optimizing the design of bacteriophage preparations for therapy. Bacteriophages (phages) are natural viral predators of bacteria, that are capable of eliminating multidrug resistant pathogens. Although phages have been proven to be highly efficient targeted antimicrobials in vitro, a limited knowledge of the complex phage-bacterium interplay in vivo, which may lead to narrow host range and resistance development, hinders the prediction of in vivo efficacy. A better understanding of the outcomes of dynamic phage-bacteria interactions is required for significant progress towards routine use of phages as antimicrobials. Towards this goal, I have led the characterization of a comprehensive phage collection against major pathogenic clones and developed murine models of gut colonization and of severe infection (bacteraemia) to prepare and test phage combinations with therapeutic potential. Data on bacterial clearance and phage kinetics in our murine models show how in vitro clearance does not immediately correlate with in vivo outcomes, pointing to different co-adaptation patterns related to the complexity of in vivo niches. At Westmead Hospital, bacteriophage and antibiotic combinations are being trialled for the treatment of severe infection in patients (2018-current). My current immediate goal is to progress the establishment of phage protocols for use in veterinary settings with the support of scientists and veterinarians at the Sydney School of Veterinary Sciences.