24 Jun Study Finds Ajoene Disrupts Biofilm in Chronic Wounds, and Enhances Antibiotic Effectiveness
MedicalResearch.com Interview with:
David Houston PhD
Senior Scientist and wound project
MedicalResearch.com: What is the background for this study?
Response: Biofilms are complex bacterial communities formed during the natural infection process as a protection mechanism and controlled by bacterial quorum sensing. These biofilm communities allow infections to spread by producing toxins that inhibit the body’s immune system, generating exopolysaccharide and changes in metabolic state that reduce the efficacy of antibiotics and activating virulence factors, which ultimately drive the spread of infection. Stopping the spread of infection by inhibition of quorum sensing has potential to manage a wide range of infections, including in wounds.
In chronically-infected wounds, the prevention of biofilm formation, disruption of mature biofilms, reduction of virulence factors and thereby the spread of infection remains clinically elusive. Quorum sensing (QS) pathways regulate microbial motility, virulence factor production and the formation and maturation of biofilms. Inhibiting QS therefore presents a potential mode of therapeutic intervention for infections.
MedicalResearch.com: What are the main findings?
Response: During the American Society of Microbiology Microbe 2019 conference, we presented data on the naturally occurring QS inhibitor, Ajoene, and its effects on motility, biofilm formation, virulence factor production and spreading infection, including activity on ex-vivo wound specific mature biofilm models.
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.
MedicalResearch.com: What should readers take away from your report?
Response: The antibacterial properties of Ajoene are already well known. Our studies confirmed that Ajoene was able to reduce secretion of virulence factors, inhibit the spread of infection and destabilised mature biofilms of Pseudomonas aeruginosa (Pa) and Staphylococcus aureus (Sa), re-sensitizing them to antibacterial agents. It also disrupted the contamination-infection continuum of an ex-vivo skin wounds and could potentially aid in the maintenance or return of chronic wounds to a healing state. This research provides insight into the mechanism behind the antimicrobial activity of Ajoene as well as providing multiple potential targets for therapeutic drug discovery.
It also disrupted the contamination-infection continuum of an ex-vivo skin wounds and could potentially aid in the maintenance or return of chronic wounds to a healing state. This research provides insight into the mechanism behind the antimicrobial activity of Ajoene as well as providing multiple potential targets for therapeutic drug discovery.
MedicalResearch.com: What recommendations do you have for future research as a result of this work?
Response: In the wound area, treatment is often impeded by infection. The work on Ajoene has led to the discovery of NX-AS-911, a series of quorum sensing inhibitors with activity against Pseudomonas aeruginosa and Staphylococcus aureus, which have shown potential in-vitro to inhibit the spread of acute infection and support management of chronic infection.
In addition, Neem has developed the NX-AS-401 series for the potential treatment of lung infections in patients with chronic respiratory conditions. It is designed to help eradicate the Pseudomonas aeruginosa bacterial infections that are the key cause of death for cystic fibrosis patients and a significant contributor to life limiting impacts in other chronic respiratory conditions. The NX-AS-401 series of compounds have a novel mechanism of action. As quorum sensing inhibitors, they disrupt communication between bacteria, thereby preventing them from forming the film that is crucial in protecting them from current anti-Pseudomonal antibiotics.
These drug candidates are now being evaluated in preparation of starting clinical studies.
Citation: ASM 2019 abstract
Ajoene a First in Class Quorum Sensing Inhibitor that Prevents, Biofilm Formation, the Production of Virulence Factors, Spreading of Infections and Modulates Established Biofilms in an Ex–Vivo Chronic Wound Infection Model
Author Block: D. M. J. Houston, D. Neef, P. Rice, D. Williams, H. Taleb, L. Jones, J. Preece, L. Sykes, W. W. Nichols, G. Dixon; Neem Biotech, Abertillery, United Kingdom
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