What are biofilms?
When a pure culture of bacteria grows in a flask the lab, they typically grow as single bacterial cells, known as a planktonic culture. However, in the real world, bacteria assemble into biofilms, aggregates of bacteria from one or more species embedded in a matrix of polysaccharides and proteins. C5-6 Technologies has isolated and studied many biofilm-forming organisms isolated from hot springs and other sources. Shown below are micrographs of just a few of the biofilms these organisms produce.
Biofilms were stained using LIVE/DEAD® BacLight™ Bacterial Viability Kit in sterile water (Molecular Probes). Dark field fluorescence microscopy was performed using a Nikon Eclipse TE2000-S epifluorescence microscope at 2000x magnification equipped with a high-pressure Hg light source and 484 nm excitation and 500 nm emission filters.
Why are biofilms a problem?
Pathogenic microbes living in biofilms – the predominant form of bacterial infections – are particularly resistant to antibiotic treatment, because bacteria in these biofilms encase themselves in a polysaccharide matrix that protects them from attack by antibiotics. Biofilms make bacteria living in them up to 1000-times more resistant to antibiotic or chemical treatment compared to free swimming bacteria. While biofilms are the target of many different therapeutic strategies that focus on preventing bacteria from forming biofilms, none have produced effective treatment against existing biofilm infections.C5-6 Technologies has several CAZymes™ that are capable of disrupting this shell by cleaving to the polysaccharide matrix produced by the biofilm bacteria. C5-6 is leveraging its deep expertise in polysaccharide enzymology to identify and work with partners to develop therapeutic enzymes that can be given as part of an antibiotic co-treatment of existing biofilm-based infections, and possibly prophylactically, to prevent biofilms from ever being established.
A new approach to treating biofilms
C5-6’s collection of proprietary polysaccharide cleaving enzymes, CAZymes, represent an entirely new mechanism of action for treating and clearing biofilm infections. We screened over 150 different CAZymes of different substrate specificities and identified eight CAZymes that efficiently cleaved the polysaccharide biofilm produced by Pseduomonas aeruginosa (P. aeruginosa), one of the leading bacteria species associated with pathogenic biofilm infections, and thereby rendered the biofilm’s underlying bacterial infection more sensitive to attack and clearance by tobramycin, a front line antibiotic. Preliminary studies also indicated that the C5-6 CAZymes inhibited the formation of new P. aeruginosa biofilms, suggesting that CAZymes could also be used prophylactically to prevent biofilm formation in patients who are likely to develop biofilm infections, such as those with cystic fibrosis.
C5-6 intends to extend the value of its intellectual property protection by screening its CAZyme collection against biofilms from other organisms besides P. aeruginosa, including methicillin-resistant Staphlococcus aureus (MRSA), Acinetobacter baumannii, Kiebsiella pneumonia, Burkholderiacenocepacia, Bordetella bronchiseptica, Streptococcus, Enterococcus, and E.coli.
CAZymes – an attractive new approach to treating biofilms.
- CAZymes’s mechanism of action – potentiating existing antibiotics to kill biofilm infections – is completely different than all other current biofilm technologies in development.
- CAZymes may prophylactically prevent new biofilm formation.
- CAZymes biologics will likely have favorable toxicology profiles.
- CAZymes, isolated from non-mammalian organisms, appear to have no known mammalian targets, thereby minimizing the chances of off-target side effects.
- CAZymes are easy to produce and have excellent stability profiles.
- CAZymes may dramatically extend the value of current antibiotics by improving and extending their effectiveness.
- CAZymes may significantly reduce the development of antibiotic resistance.
C5-6 is seeking pharmaceutical partners to help accelerate the preclinical development of its CAZyme candidates as co-treatments against biofilm infections. Our goal is to identify CAZyme lead candidates that are effective against each of the different, major, pathogenic bacterial infections when administered as a co-treatment with an existing antibiotic.
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