Phosphorylated and Branched DPD Analogs as Quorum Sensing Inhibitors in Bacteria

University of Maryland
posted on 08/18/2010

Inventors at the University of Maryland, College Park have created unique QS inhibiting AI-2 (Autoinducer-1) based analogs that disrupt biofilm formation and consequently bacterial pathogenicity. Researchers have shown for the first time that phosphorylated branched DPD (dihydroxy-pentane-dione) AI-2 analogs are QS antagonists. They can replace the previously used AHL inhibitors which are species specific. The ubiquitous AI-2 is capable of inhibiting and modulating QS among multiple pathogenic species simultaneously. These quorum quenching analogs could potentially have extensive applications in both medical and non-medical fields.

Suggested Uses

- New generation antimicrobial therapy drug that prevents virulence in diverse pathogenic bacteria such as Vibrio Cholerae, Salmonella typhimurium and Pseudomonas aerunginosa.
- Easy to use tool-kit with specific analogs ideal for commercialization.
- Ideal for treating gut infections where analogs could differentiate between the pathogens from mutualistic organisms using differentially constructed AI-2 analogs.
- Utility in Surgical implants and catheters prone to biofilm induced infections.
- Potential assistance in Bio-fermentation.
- Marine Biofilm formation prevention.

Advantages

- Broad species or species-specific QS inhibition.
- Based on the C1-alkyl chain length in the AI-2 analogs, this system could potentially modulate QS en mass or selectively.
- The ability to selectively target pathogenic bacteria from the non-pathogenic ones has important clinical implications.
- The innocuous AI-2 analogs pose less evolutionary pressure on bacteria than other current bacteriostatic or bacteriocidal anti-microbials responsible for drug resistant strains.

Detailed Description

Antibiotic resistance is a critical issue plaguing public health. The development of alternative antimicrobial therapies like Quorum Sensing inhibitors could be an effective solution. Quorum Sensing (QS) is a bacterial cell to cell communication system used by decentralized group of bacteria to coordinate behavior including motility, substrate attachment, biofilm formation and pathogenicity. This phenomenon allows broad spectrum bacterial species to interact in a communal fashion discouraging antibiotic efficacy. Disruption of this process could potentially lead to the inhibition of microbial growth.

Inventors at the University of Maryland, College Park have created unique QS inhibiting AI-2 (Autoinducer-1) based analogs that disrupt biofilm formation and consequently bacterial pathogenicity. Researchers have shown for the first time that phosphorylated branched DPD (dihydroxy-pentane-dione) AI-2 analogs are QS antagonists. They can replace the previously used AHL inhibitors which are species specific. The ubiquitous AI-2 is capable of inhibiting and modulating QS among multiple pathogenic species simultaneously. These quorum quenching analogs could potentially have extensive applications in both medical and non-medical fields.

File Number: LS-2010-005

Web site: http://otc.umd.edu