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. Unfortunately, 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. Addressing antimicrobial resistance is critical and we believe it is equally important to study resistant bacteria under clinically relevant conditions such as high-bacterial density infections.
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 infections.
Antibiotic (ciprofloxacin) and synthetic peptides (DJK-5, 1018) mono- and combinatorial therapy in a murine cutaneous abscess model and clinical drug-resistant Pseudomonas aeruginosa.
Our lab also uses novel antimicrobial technologies that exploit nutrient uptake systems to overcome bacterial resistance mechanisms and to provide novel insights for design and delivery of new therapies. 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 various pathogenic bacterial strains using various biological, genomic, and biochemical methods. The idea is to disguise an antimicrobial compound as a natural food resource to facilitate drug uptake.
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
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