Centre for Superbug Solutions

Charactering the efficacy of novel chemical entities in multi-drug resistant bacteria

Supervisors: Professor Mark Walker (mark.walker@uq.edu.au); Dr David De Oliveira (d.deoliveira@uq.edu.au)

Antimicrobial resistance (AMR) is currently a significant global health concern and is projected to be the leading cause of death by 2050. Many first, second and last-line antibiotics are no longer effective in the treatment of severe bacterial infection. As such, new antimicrobials are urgently required. Previous work from our group has demonstrated that compounds with a core 8-hydroxyquinolone structure exhibit broad range antimicrobial activity against a spread of clinically relevant drug-resistant bacteria. This Honours project will comprehensively evaluate the antimicrobial efficacy of next-generation, 8-hydroxyquinolone core containing structures against a select range of clinically relevant drug-resistant bacterial pathogens. This research has the potential generate an innovative treatment for patients suffering drug-resistant bacterial infection.

How antibiotic resistant uropathogenic E. coli cause urinary tract infection

Supervisors: Professor Mark Schembri (m.schembri@uq.edu.au), Dr Minh-Duy Phan (m.phan1@uq.edu.au)

Urinary tract infections (UTIs) are one of the most common infectious diseases, with a global annual incidence of ~400M cases. UTI is also a major precursor to sepsis, which affects ~50M people worldwide each year, with a mortality rate of 20-40% in developed countries. Uropathogenic E. coli (UPEC) is the major cause of UTI and a leading cause of sepsis. The last decade has seen an unprecedented rise in antibiotic resistance among UPEC, resulting in high rates of treatment failure and mounting pressure on healthcare systems. This project will use advanced molecular genetics and infection models to examinehow UPEC cause disease and become resistant to antibiotics, with a goal to identify new approaches to treat and prevent infection.

How E. coli cause life-threatening infections in infants

Supervisors: Professor Mark Schembri (m.schembri@uq.edu.au), Dr Nhu Nguyen (kn.nguyen@uq.edu.au)

Neonatal meningitis is a devasting disease with high rates of mortality and neurological sequelae. E. coli is the primary cause of meningitis in preterm neonates and the second most common cause of neonatal meningitis. Despite this, we have limited knowledge about the global epidemiology of E. coli that cause neonatal meningitis, genomic relationships between different strains, and mechanisms that enable E. coli to cause severe infection in new-born infants. This project will identify and characterise common genomic features of E. coli that cause neonatal meningitis, and employ molecular microbiology methods in conjunction with animal models to understand disease pathogenesis and antibiotic resistance. Our goal is to develop new diagnostic and therapeutic interventions to prevent this life-threatening disease.

Investigating the role of host lipids in Salmonella infections

Machine learning in drug discovery - Data mining and validation

Machine learning in drug discovery - Data modelling and prediction

Synthesis of antibiotic-derived conjugates

Synthesis of antibiotic-derived fluorescent probes

Understanding the genetic basis for Salmonella Typhimurium biofilm formation under infection relevant conditions

Supervisors: Dr Jessica Rooke (j.rooke@imb.uq.edu.a u), Professor Ian Henderson (i.henderson@imb.uq.edu.au)

Salmonella enterica is a globally disseminated pathogen that causes infections in humans, animals, and plants. As part of this infectious lifecycle, S. enterica often forms biofilms that are capable of withstanding routinely used antibiotics. Various environmental signals have been shown to induce biofilm formation, and we have identified that host lipids induce robust biofilm formation in vitro. However, the precise mechanism for biofilm formation under these conditions remain unknown. In this project, we aim to elucidate the genetic determinants of S. enterica biofilm formation in response to host lipids, to further understand this phenomenon and to develop novel therapeutics to treat infections that are complicated by biofilm formation.

Using genetics to understand antimicrobial resistance

Supervisors: Professor Ian Henderson (i.henderson@imb.uq.edu.au), Dr Von Torres (v.torres@uq.edu.au)

Antimicrobial resistance (AMR) is a global issue as drug-resistant bacterial infections have been estimated to contribute to at least ~5 million deaths in 2019 alone and is expected to reach 10 million deaths annually by 2050. The genetic mechanisms of drug resistance in bacteria are diverse and complex but elucidating these are vital for developing novel therapeutics and control strategies. Building on previous work, we aim to further explore and validate findings of genes involved in antibiotic resistance in Gram-negative bacteria. The student undertaking this project will learn fundamental concepts in molecular microbiology and use a variety of techniques including: bacterial strain culturing and maintenance, antimicrobial susceptibility testing, phenotypic and biochemical assays.