Identifying novel antimicrobials against bacteria resistant to traditional antibiotics

--------------------------------------------- Background: --------------------------------------------- Antimicrobial resistance is a key global issue, with resistance to important antibiotics increasing yearly, resulting in 1.14 million deaths in 2021 alone. We treat bacterial infections with antimicrobials. However, pathogens rapidly develop resistance to antimicrobials by acquiring resistance genes, reducing treatment efficacy. This is compounded by the extensive genetic diversity displayed by pathogens which complicates the traditional antimicrobial approaches. Fortunately, bacteria themselves produce antimicrobials called ‘bacteriocins’, which they use in bacterial warfare. The goal of this project is to leverage these naturally-produced bacteriocins against key antimicrobial resistant pathogens. Currently, we have a list of 7 bacteriocin classes encoded by the #1 priority multi-drug resistant pathogen globally, Klebsiella pneumoniae. Using genomics, we have predicted the production of, and susceptibility of clinical isolates to these bacteriocins, which now requires laboratory validation. --------------------------------------------- In this project, you will: --------------------------------------------- ‎ ‎ 1) Test K. pneumoniae bacteriocin producers against clinical isolates to determine ‎ ‎ ‎ a. If the bacteriocins kill antimicrobial resistant K. pneumoniae ‎ ‎ ‎ b. The activity spectra and range of bacteriocin killing ‎ 2) Purify bacteriocin proteins and confirm their identity with peptide sequencing ‎ ‎ ‎ a. Use genomics to match these peptide sequences back to our predictions --------------------------------------------- Outcomes for you as a student on this project: --------------------------------------------- ‎ 1) Laboratory and microbiology expertise including handling the key bacterial pathogen, K. pneumoniae ‎ 2) Gain experience with bioinformatics and genomics workflows informing your work ‎ 3) Contribute to the discovery of novel antimicrobials for treating antimicrobial resistant pathogens ‎ 4) Opportunity to contribute as a co-author to a publication --------------------------------------------- Resources you will be supported by: --------------------------------------------- ‎ • Global experts in Klebsiella pneumoniae, antimicrobial resistance and bacterial pathogenesis: Dr. Ben Vezina and A/Prof. Dr Kelly Wyres ‎ • Professional microbiology laboratories situated at The Department of Infectious Diseases, with close ties to Alfred Health. ‎ • As we have already predicted antimicrobial activity, this project is likely to be high-yielding as the laboratory experiments are highly focused. ‎ • Handling a globally-unique collection of clinical K. pneumoniae isolates ‎ • Access to a high-performance supercomputer --------------------------------------------- Skills and interests you will bring --------------------------------------------- ‎ • Required ‎ ‎ ‎ o Microbiology or wet laboratory experience ‎ ‎ ‎ o Interest in antimicrobial research ‎ ‎ ‎ o Interest in bioinformatic skill development ‎ • Ideal but not required ‎ ‎ ‎ o Experience with command line and any coding language ‎ ‎ ‎ o Antimicrobial resistance assays