The global surge in antimicrobial resistance is alarming, with emerging and spreading resistance mechanisms underscoring the critical need for innovative anti-infective strategies. A frequently overlooked aspect is the prevalence of high-density bacterial communities and adaptively resistant biofilms in bacterial infections. Conventional antibiotic administration approaches often prove ineffective against these complex infection types, and there is a notable scarcity of novel strategies in development to tackle this pressing issue.
How can we target antibiotic resistant and tolerant bacteria?
We find ourselves in an era where bacteria have evolved resistance to multiple antibiotics, presenting a formidable threat to human health. Compounding this challenge, bacteria can thwart the lethal impact of antibiotics by thriving within a protective polymeric matrix known as biofilms. The safeguarding of antimicrobials within these organized bacterial communities is referred to as ‘adaptive resistance,’ and it is increasingly recognized as a significant contributor to the diminished therapeutic effectiveness of antibiotics.
Host defense peptides to target resistant pathogens
Our research is dedicated to advancing novel therapeutics and nanomedicines centered on natural host defense peptides. These peptides exhibit synergistic effects with antibiotics, effectively targeting various individual pathogens within biofilms (microbial communities) and infections. Our focus extends to understanding how these peptides augment the activity of antibiotics, particularly in the elimination of polymicrobial infections.
The peptides we investigate specifically target bacterial stress responses, persister-based resistance, and the outer membrane permeability barrier. In our commitment to exploring the potential of host defense peptides as innovative adjuvant therapies, we conduct advanced pre-clinical studies that involve examining peptide-antibiotic combinations. These studies aim to evaluate the efficacy of such combinations in treating polymicrobial infections, encompassing both lung and skin infections.
Collaborators include Prof. Robert Hancock, A/Prof. Annelise Barron and many more …
Nanoparticles to overcome multidrug resistance
Metal and metal oxide nanoparticles have emerged as compelling antimicrobial agents in the battle against multidrug-resistant bacteria. Notably, silver nanoparticles have demonstrated broad-spectrum antimicrobial efficacy. Currently, our research is dedicated to exploring the potential of silver and gold nanoparticles in combating multidrug-resistant strains of P. aeruginosa and S. aureus. A key emphasis in our investigations involves biofilm-forming bacteria, with a particular objective of developing therapeutic strategies for patients afflicted by oral mucositis.
Bacterial stress responses as novel targets
We are exploring the viability of stress responses as potential therapeutic targets. Our focus centers on the investigation of downstream effectors associated with the stringent stress response in various ESKAPE pathogens.
Improving drug delivery strategies
Our laboratory is dedicated to exploring innovative antimicrobial technologies that leverage nutrient uptake systems to overcome bacterial resistance mechanisms. Our research involves the synergistic combination of antibiotics with short amino acids, aiming to exploit individual drug uptake systems for enhanced efficacy against pathogenic strains. To refine drug delivery strategies, we employ diverse biological, genomic, and biochemical methods to scrutinize drug/nutrient uptake mechanisms in Pseudomonas aeruginosa.
Additionally, our investigations extend to the exploration of prodrugs designed to activate specifically in the presence of an ongoing infection. These studies yield valuable insights for the design and delivery of new therapeutic interventions.
Most of this work is done in collaboration with A/Prof. Allan Gamble and Prof. Sarah Hook.
How do bacteria develop resistance to multiple antibiotics simultaneously?
In collaboration with Prof. Iain Lamont, Prof. Weihui Wu, and A/Prof. Yongxin Jin we are investigating the best antibiotic combinations that could prevent resistance development. We are interested in how bacterial pathogens can develop resistance to two antibiotics simultaneously.
Read more about our recent research here:
Pletzer D, Mansour SC, Hancock REW. 2018. Synergy between conventional antibiotics and antibiofilm peptides in a murine, sub-cutaneous abscess model caused by recalcitrant ESKAPE pathogens. PLoS Pathog. 14(6):e1007084
