Ajoene found to reduce virulence factor secretion, destabilise mature bacterial biofilms, allowing re-sensitisation to antibacterial agents
Neem Evaluating Drug Candidates based on Ajoene for Clinical Evaluation Against Wound Infections
Cardiff, UK|24 June 2019
Neem Biotech, a company focused on developing novel solutions to address antimicrobial resistance, announced today the presentation of data demonstrating the effectiveness of Ajoene against the spread of infection in chronic wounds at ASM Microbe 2019 in San Franciso (20-24 June). Ajoene is a quorum sensing inhibitor found naturally in garlic. Quorum sensing (QS) pathways regulate microbial motility, virulence factor production, and the formation and maturation of biofilms, providing a potential mode of therapeutic intervention. Neem has identified and synthesised novel compounds inspired by Ajoene. These candidate compounds are being evaluated for clinical studies.
“There is an urgent need for new avenues of treatment in chronically-infected wounds. So far, the ability to prevent biofilm formation, disruption of mature biofilms, reduction of virulence factors and thus the spreading of infection remains clinically elusive,” said Dr. David Houston, Senior Scientist and wound project lead at Neem Biotech. “The antibacterial properties of Ajoene are well known. This research provides insight into the mechanism behind this activity as well as multiple potential targets for therapeutic drug discovery.”
In the studies, the effects of Ajoene on planktonic bacteria and biofilms of Pseudomonas aeruginosa (Pa) and Staphylococcus aureus (Sa) were tested using QS inhibition, biofilm formation and eradication assays. Ajoene was also tested against novel biofilm skin and chronic wound spreading infection models using a mature Pa + Sa biofilm consortium.
Ajoene inhibited QS in Pa (80% at 75 μM) and Sa (33 mm zone of inhibition at 3 mM) and inhibited the formation of biofilms of Pa (IC50 31 ± 10 μM) and Sa (1 ± 0.5 μM). Pre-treatment with Ajoene enhanced the susceptibility of Pa and Sa iodine, in vitro. Ajoene reduced the secretion of hemolysin in Sa of lasB, RL, pyocyanin and proteases in Pa. Ajoene reduced microbial viability in a biofilm infection model of ex-vivo porcine skin (>5 log reduction of colony forming units of both Pa and Sa). A clinically relevant Ajoene-loaded hydrogel prevented the spread of bacteria from the initial inoculation site in the chronic wound ex vivo model.