Genomic and experimental analysis of antimicrobial resistance and hypervirulence convergence in Klebsiella pneumoniae

Antimicrobial resistance (AMR) 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, bacterial pathogens have rapidly developed resistance to many antimicrobials, typically via acquiring AMR genes on mobile DNA (such as plasmids), and thereby reducing treatment efficacy. <!--break--> Klebsiella pneumoniae has been recognised by health agencies including the World Health Organisation as a top priority multi-drug resistant pathogen that is a leading cause of healthcare-associated infections globally. Many of these strains carry plasmids with AMR genes. Some strains of K. pneumoniae also carry plasmids with virulence genes that can enhance disease severity (i.e. ‘hypervirulence’). While antimicrobial resistance and virulence have typically been segregated in different strains, but recent evidence shows increasing convergence of these two traits (e.g. a strain with an AMR plasmid acquiring a virulence plasmid, or vice versa). Concerningly, there are also growing reports of AMR and virulence plasmids recombining to form a single plasmid with both traits, potentiating infections that are highly deadly and difficult to treat effectively. <!--break--> We have clinical isolates from Alfred Health with hypervirulence and multi-drug resistance phenotypes. <!--break--> <!--break--> In this project, you will: 1) Obtain genomes that display convergence of antimicrobial resistance and hypervirulence 2) Use genomics to analyse the evolutionary history of these convergent genomes/plasmids 3) Perform laboratory experiments to transfer antimicrobial resistance plasmids (ESBL) to hypervirulent recipients via conjugation or vice versa a. Passage the recipient over time and perform DNA sequencing to determine if convergent recombination between the plasmids occurs <!--break--> Skills and interests you will bring: 1) Required o Interest in evolution and bioinformatics o Experience with microbiology 2) Ideal but not required o Experience with command line or any coding language <!--break-->