Antimicrobial resistance and nanomedicines

Antimicrobial resistance is rising all over the world and new resistance mechanisms are emerging and spreading, highlighting the importance for novel anti-infective strategies. Often neglected is the fact that bacterial infections can involve high-density bacterial communities as well as bacteria growing in adaptively resistance biofilms. Antibiotic administration strategies often fail to cure these types of infections and there are relatively few novel strategies under development to address this important issue.

How can we target antibiotic resistant and tolerant bacteria?

We are in era where bacteria have developed resistance to multiple antibiotics and pose one of the greatest threats to human health. In addition, bacteria can overcome the deadly effects of antibiotics through their growth in a protective polymeric matrix, so-called biofilms. The protection of antimicrobials in these structured bacterial communities is termed ‘adaptive resistance’ and has been proposed to also play a major role in reducing therapeutic effectiveness of antibiotics.

Host defense peptides to target resistant pathogens

Our work focuses on novel therapeutics and nanomedicines, based on natural host defence peptides, that work synergistically with antibiotics against several individual pathogens in biofilms (microbial communities) and infections, and study how they enhance the activity of antibiotics to eliminate polymicrobial infections. Peptides target the bacterial stress response, persister-based resistance, and the outer membrane permeability barrier. To further investigate the potential of host defence peptides as novel adjuvant therapies, we perform advanced pre-clinical studies examining peptide-antibiotic combinations to treat polymicrobial (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 gained quite some interest as antimicrobials to target multidrug resistant bacteria. Particularly, silver nanoparticles have shown to possess broad-spectrum antimicrobial activity. At the moment, we explore silver and gold nanoparticles to treat multidrug resistant P. aeruginosa and S. aureus. A specific focus of our research with nanoparticles addresses biofilm-forming bacteria with the goal to treat patients suffering from oral mucositis.

Bacterial stress responses as novel targets

We research whether stress responses can be used as therapeutic targets. In particular, we investigate downstream effectors of the stringent stress response in P. aeruginosa.

Improving drug delivery strategies

Our lab investigates novel antimicrobial technologies that exploit nutrient uptake systems to overcome bacterial resistance mechanisms. We work on combining antibiotics with short amino acids and study whether individual drug uptake systems can be hijacked to enhance efficacy in pathogenic strains. To improve drug delivery strategies, we investigate drug/nutrient uptake mechanisms in Pseudomonas aeruginosa using various biological, genomic, and biochemical methods.

We also investigate various prodrugs that only activate in the presence of an ongoing infection. Our studies provide novel insights for design and delivery of new therapies.

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 Pathog14(6):e1007084