Bacterial infections remain a leading cause of death worldwide. Despite antibiotics and supportive therapies, bacterial infections can lead to life-threatening conditions. The alarming increase in antibiotic resistance highlights the urgent need for new and better antibiotics and has more recently shifted the focus towards host-directed therapies that enhance the antimicrobial defence as potential adjunct and/or alternative approaches. Inflammation is essential for host control of pathogens, yet unchecked inflammation drives acute organ damage and chronic disease. Thus, understanding of the mechanisms that regulate and terminate inflammation, and thereby re-establish homeostasis and ensure host survival, is important when devicing therapeutic interventions that are directed towards improving host defence mechanisms against pathogens.

Our research focuses on:

i) elucidating molecular and cellular mechanisms that underpin successful control of bacterial pathogens and effective inflammatory responses. The overall goal is to provide the basis for host-directed interventions in challenging bacterial infections.

Specifically, we are

  • Elucidating molecular mechanisms of how pathogens are recognised and how this translates into cellular programs of inflammation and antimicrobial defence. 

  • Identifying factors that regulate inflammation and host defence against bacterial pathogens at the molecular, cellular and tissue level.

  • Deciphering the immune landscape of infected tissues to better define what constitutes successful control of pathogens.  

This research encompasses molecular and cell biological analyses, cellular and in vivo infection models, as well as analyses of patient cohorts. We utilise global and targeted gene and protein expression analyses, high-resolution cellular and tissue imaging, and flow cytometry to define the mechanisms that orchestrate successful immune control of invading pathogens while safeguarding and repairing the integrity of the infected tissue. We focus on sepsis and tuberculosis, diseases with immense global burden, mortality, and potential long-term impact on quality of life in survivors.

ii) characterisation of how new antimicrobial compounds and existing antibiotics exert their effects on pathogenic bacteria. The overall goal is to identify potential new lead compounds and putative molecular drug targets that will enable the development of new or improved treatments for challenging bacterial infections and overcome the threat posed by antimicrobial resistance.

Specifically, we are:

  • Investigating mechanisms by which antibiotics and antimicrobial compounds enter bacterial cells.

  • Identifying and characterising molecular targets and mechanisms of action of antimicrobial leads.

  • Identifying mechanisms of bacterial resistance to antibiotics and antimicrobial lead compounds.

This research employs molecular and cellular microbiology, transcriptome and proteome analyses, molecular modelling, as well as bioinformatics-driven interrogation of genomic information from clinical specimen collections to identify desirable features of new generations of antibiotics that will overcome the threat posed by treatment-resistant bacterial pathogens. Currently, our main focus is Mycobacterium tuberculosis, the causative agent of causes tuberculosis, an infectious disease that continues to pose significant threats to public health and remains a leading cause of death globally.