References and Publications

Publications table of content

The 2FX-complex
Dysbiosis
General conclusions on Anti-adhesive Strategies
Further reading

The 2FX-complex

Discovery and characterization of the molecules

In many cultures, the application of the inner gel of Aloe vera barbadensis leaves for healing wounds and treating skin and mucosal infections has been documented. A collaboration between BioClin and the Free University University of Amsterdam revealed the promising anti-adhesive activity of the 2FX-complex. The 2FX-complex effectively blocks the adhesion of pathogenic microbes to human epithelial cells and tissues. The 2FX-complex is made up of large, negatively-charged polysaccharides obtained by molecular filtration and purification of the inner gel.^1,2,3

Dysbiosis

How microbial imbalance can lead to infection and inflammation

The disturbance of the healthy microbiota by intruding pathogens is known as dysbiosis. These pathogens start to compete with the beneficial bacteria by adhering to our epithelial tissues. Sites of entry in human hosts include the skin, the urogenital tract, the digestive tract, the respiratory tract and the eyes. Adherence of pathogenic microbes is the essential first step in the process of colonization and infection^5,6.This results in an inflammatory response of our immune system to the pathogenic intruder, giving rise to symptoms such as redness, swelling, itching and/or a burning sensation.

General conclusions on Anti-adhesive Strategies

Adapted from Krachler et al ⁷
• Bacterial adherence to host tissues is a universally required early step for establishing infections and, thus, targeting this process holds promise as an alternative approach to conventional antibiotics for treating bacterial infections.
• Because anti-adhesive compounds clear rather than kill microbes, there is no selective pressure on the pathogen to develop resistance to this process, and development of resistance is highly unlikely.
• Several compounds show promise, but wider use of anti-adhesion therapy will depend on the discovery of new anti-adhesion drug targets and on compounds with better affinity, stability and bioavailability.
• Antibiotic-resistant strains of pathogens necessitate development of alternative means to prevent and treat bacterial infections.

• Zopf, Lancet 1996, Oligosaccharide anti-infective agents. Describes oligosaccharides (large sugars) from human breast milk, mono- and polyvalent polysaccharides (both natural and biotechnologically developed therapeutics)¹⁰. The authors consider topical applications such as vaginal and nasopharyngeal as promising.

• Sharon 2000, Glycoconjugate journal. Safe as mother’s milk: carbohydrates as future anti-adhesion drugs for bacterial diseases¹¹. Describes polysaccharides from mothers milk as safe potential future anti-adhesion drugs for bacterial diseases.

• Krachler 2013, Virulence. Targeting the bacteria-host interface: strategies in anti-adhesion therapy¹². Natural mannose derivatives are well-known for their anti-adhesive effect. This paper describes new mannose-derived compounds were developed with enhanced FimH binding and improved systemic availability and stability.

References:
1. Van Dijk W, Goedbloed AF, Koumans FJR. 2002. Negatively charged polysaccharide derivable from Aloe Vera. Publication Date:29.09.2004 Filing Date:23.12.2002. EP01205253. European patent office.
2. Van Dijk W, Bruyneel B, Van het Hof B, Nietfeld M, De Jong J, Celi P, Nijrolder I, Viegas C, Niessen H, Namavar F. 2004. A charged polymannose-containing fraction of Aloe vera gel inhibits binding of Helicobacter pylori to salivary mucin. Document on file. Amsterdam, The Netherlands.
3. Van Dijk W. 2006. Further characterization of negatively charged polysaccharides isolated from concentrated Aloe vera gel with regard to antibacterial properties and molecular structure. Document on file. Amsterdam, The Netherlands.
4. Finlay BB. 1997. Exploitation of Mammalian Host Cell Functions by Bacterial Pathogens. Science (80-. ). 276:718–725.
5. Ofek I, Hasty DL, Doyle RJ. 2003. Bacterial Adhesion to Animal Cells and Tissues. American Society for Microbiology Press, Washington, DC.
6. Krachler AM, Orth K. 2013. Made to Stick: Anti-Adhesion Therapy for Bacterial Infections. Microbe Mag. 8:286–290.
7. Kelly CG, Younson JS. 2000. Anti-adhesive strategies in the prevention of infectious disease at mucosal surfaces. Expert Opin. Investig. Drugs 9:1711–21.
8. Sharon N. 2006. Carbohydrates as future anti-adhesion drugs for infectious diseases. Biochim. Biophys. Acta 1760:527–37.
9. Zopf D, Roth S. 1996. Oligosaccharide anti-infective agents. Lancet 347:1017–21.
10. Sharon N, Ofek I. 2000. Safe as mother’s milk: carbohydrates as future anti-adhesion drugs for bacterial diseases. Glycoconj. J.
11. Krachler AM, Orth K. 2013. Targeting the bacteria-host interface: strategies in anti-adhesion therapy. Virulence 4:284–94.