Centre for Superbug Solutions

Supervisors: Dr Johannes Zuegg (j.zuegg@imb.uq.edu.au)

The Community for Open Antimicrobial Drug Discovery (CO-ADD) is maintaining a web-based information system, for the antimicrobial and chemistry data it collected over the last 5 years. The dataset is used to build various machine learning methods for the prediction of antimicrobial activity and enhance the discovery of novel antibiotic against multi-drug resistant pathogen. The project aims to enhance the dataset with additional data from public sources, by using data-mining methods and large language models (like Llama2) to extract structured data from the public sources. 

Supervisors: Professor Mark Schembri (m.schembri@uq.edu.au)

Biofilms are surface-attached clusters of bacteria encased in an extracellular matrix and are significantly associated with increased antibiotic resistance. This project will apply molecular microbiology methods to understand the structure, function and regulation of biofilms produced by uropathogenic E. coli that cause urinary tract infections, and investigate new strategies to disrupt biofilms. The project will build skills in cutting edge genetic screens, molecular microbiology, genome sequencing, bioinformatics, microscopy, imaging and animal infection models. Students with an interest in microbiology, bacterial pathogenesis and antibiotic resistance are encouraged to apply.

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.

Supervisors: Professor Waldemar Vollmer (w.vollmer@imb.uq.edu.au)

Gram-negative bacteria have an outer membrane that is tightly connected with the underlying peptidoglycan cell wall and protects the cell from many toxic molecules and even antibiotics that work against Gram-positive bacteria. We know little about how growing and dividing bacteria coordinate the biogenesis of the outer membrane with the growth of the peptidoglycan layer. The projects will build on our recent discoveries to dissect the dynamic linkages between the outer membrane and peptidoglycan, to identify weaknesses in the assembly process that may be exploited in the future by new antibiotics. The student undertaking the project will learn state-of-the art techniques in microbiology and molecular biology on molecular targets that are of interest for antibiotic drug discovery.

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.

Supervisors: Professor Mark Schembri (m.schembri@uq.edu.au)

Urinary tract infections (UTIs) are one of the most common infectious diseases, with a global annual incidence of approximately 400 million cases. UTI is also a major precursor to sepsis, which affects about 50 million 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, and associated with high rates of antibiotic resistance. This project will explore how UPEC cause disease, with a goal to identify new approaches to treat and prevent infection. Students with an interest in microbiology, bacterial pathogenesis, animal infection models and antibiotic resistance are encouraged to apply.

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

Supervisors: Professor Waldemar Vollmer (w.vollmer@imb.uq.edu.au)

The current spread of antimicrobial resistance is a major concern for public health because the pipeline of antibiotic drug development is almost empty. Hence, there is an urgent need to discover new ways to inhibit and kill disease-causing bacteria by new drugs to be developed. The bacterial cell wall envelope is an ideal target for antibiotics because it is essential for a bacterial cell and not present in humans, and target sites are better accessible for drugs than internal ones. Indeed, some of the most successful antibiotics in history (e.g., the beta-lactams) inhibit bacterial cell wall synthesis. The student will generate a web-based platform of key cell envelope proteins and perform bioinformatic analysis of their distribution and abundance, to predict promising new target sites for antibiotic action (computational part). The student will then validate one selected target site identified, using genetic and molecular biology methodologies in important bacterial pathogens (experimental part).

Supervisors: Dr Johannes Zuegg (j.zuegg@uq.edu.au), Dr Davy Guan (d.guan@imb.uq.edu.au)

Supervisors: Dr Johannes Zuegg (j.zuegg@uq.edu.au), Dr Davy Guan (d.guan@imb.uq.edu.au)

Supervisors: Dr Johannes Zuegg (j.zuegg@imb.uq.edu.au)

A rapid determination if an infection is caused by a drug-resistant pathogens is becoming more and more a medical issue in hospitals. One option is to use whole genome sequencing (WGS) together with machine learning models to predict the resistance profile of the bacteria. The Community for Open Antimicrobial Drug Discovery (CO-ADD) has collected more than 800 multi-drug-resistant bacteria, together with their whole genome sequence and their activity/resistance against antibiotics used in the clinic. The project is to use the collected data and build predictive models, starting from published machine learning methods and develop improved deep learning methods. 

Supervisors: Professor Waldemar Vollmer (w.vollmer@imb.uq.edu.au)

Gram-negative bacteria have a complex cell envelope with a thin peptidoglycan layer and an outer membrane. Different multi-protein machineries expand the peptidoglycan layer during length growth and cell division, and trans-envelope machines export phospholipids, LPS and outer membrane proteins through the peptidoglycan to their final destination in the outer membrane. How these machines work and are coordinated with each other is poorly understood. The project aims to reconstitute key steps in cell envelope biogenesis in the test tube as tools to investigate their structures and functioning, and assay development for the screening for new antibiotic molecules. The student will learn advanced biochemical techniques using membrane systems with complex substrates and advanced assays.

Supervisor: Profesor Mark Blaskovich (m.blaskovich@uq.du.au)

Supervisor: Professor Mark Blaskovich (m.blaskovich@uq.du.au)

Supervisors: Dr Brian Forde (b.forde@uq.edu.au)

Elizabethkingia anophelis is an opportunistic pathogen capable of causing diverse severe and complex infections, including sepsis and neonatal meningitis. E. anophelis has been linked to prolonged community-associated outbreaks spanning multiple years but is predominantly associated with nosocomial infections, especially among immunocompromised patients and those with underlying comorbidities. Complicating treatment is the inherent resistance of these bacteria to a broad spectrum of antibiotics, including penicillins, β-lactams, β-lactamase inhibitors, cephalosporins, carbapenems, and polymyxins. Consequently, infections caused by E. anophelis exhibit a mortality rate ranging from 18% to 70%. The potential for E. anophelis to establish persistent colonise in individuals is concerning and presents a significant risk for onward transmission, particularly in cases of perinatal vertical transmission from mother to neonate. Despite these concerns the genomics and clinical significance of E. anophelis remains poorly understood. This project provides a unique opportunity for a comprehensive genomic analysis of a clonal lineage within a single individual, improving our understanding of Elizabethkingia infections and revealing how this organism can persistently colonise its host and cause frequent intermittent BSI despite extensive exposure to multiple different antibiotics. 

Supervisors: Professor Mark Schembri (m.schembri@uq.edu.au)

Antimicrobial resistance (AMR) is a major threat to global human health. In 2019 alone, there were an estimated 4.95 million deaths associated with bacterial AMR, with uropathogenic E. coli (UPEC) a leading pathogen associated with urinary tract infections, sepsis and high rates of antibiotic resistance. This project will use cutting edge genetic screens, molecular microbiology, genome sequencing and bioinformatics to understand how plasmids contribute to the spread of antibiotic resistance in UPEC. Students with an interest in microbiology, bacterial pathogenesis and antibiotic resistance are encouraged to apply.

Supervisors: Dr Jessica Rooke (j.rooke@imb.uq.edu.au), 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.

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.