Method To Prevent Biofilm Formation in Various Clinical Settings (Contact Lenses, Wounds, Cystic Fibrosis, etc.)

Tech ID: 04-08

Video
New Method Attacks Bacterial Infections of Contact Lenses

Background
Researchers at National Jewish Health have determined that actin originating from necrotized human neutrophils serve as a biological matrix in the formation of microbial biofilms in the airways of cystic fibrosis (CF) patients.  Since biofilm formation allows for the survival of microbial organisms in the airways and is also associated with increased morbidity and mortality, targeting actin could be the basis for the development of a potential therapy for CF.

 

Technology
Targeted therapy for preventing or reducing biofilm formation in cystic fibrosis, cystitis, dental caries, wounds, and acne etc.
Prevention of microbial biofilm development on contact lenses, and other medical devices.

 

Advantages of Invention
This therapy, focused on biofilm prevention or degradation, is particularly applicable for early stage CF in young patients when antimicrobial agents are only partially effective at best.

 

State of Development
Our scientists have shown the following in vitro:

Biofilm development of P. aeruginosa is enhanced with:

  • the addition of human viable neutrophils and correlates with an increase in the number of necrotic neutrophils.
  • the addition of neutrophils lysates and particularly with monomeric actin (G-actin)
Biofilm development of P. aeruginosa is reduced with:
  • the addition of neutrophils lysates depleted of actin microfilaments (F-actin).
  • the addition of compunds that promotes the depolymerization of F-actin, such as gelsolin or charged poly(amino acids).

Our scientists have developed charged poly amino acids that promotes the depolymerization of actin and reduced biofilm development of P. aeruginosa in vitro.

In a clinical rabbit model of contact lens–related P. aeruginosa infection, our scientists have shown that the use of polyaspartic acid disrupt pathogenic biofilms formed on contact lenses and reduce corneal infections. The effect was enhanced when used with DNAse.

 

Further R&D Required
Using the state grant to identify the most effective charged poly(amino acids) at disrupting biofilms and testing such compounds on infected contact lenses, and in animal models of eye and skin infections.

 

Publications

  • Walker, T. S., K. L. Tomlin, G. S. Worthen, K. R. Poch, J. G. Lieber, M. T. Saavedra, M. B. Fessler, K. C. Malcolm, M. L. Vasil, and J. A. Nick. "Enhanced Pseudomonas Aeruginosa Biofilm Development Mediated by Human Neutrophils." Infection and Immunity 73.6 (2005): 3693-701. Print. PMID:  15908399

  • Parks, Q. M., R. L. Young, K. R. Poch, K. C. Malcolm, M. L. Vasil, and J. A. Nick. "Neutrophil Enhancement of Pseudomonas Aeruginosa Biofilm Development: Human F-actin and DNA as Targets for Therapy." Journal of Medical Microbiology 58.4 (2009): 492-502. Print. PMCID: PMC2677169.

  • Robertson, D. M., Q. M. Parks, R. L. Young, J. Kret, K. R. Poch, K. C. Malcolm, D. P. Nichols, M. Nichols, M. Zhu, H. D. Cavanagh, and J. A. Nick. "Disruption of Contact Lens-Associated Pseudomonas Aeruginosa Biofilms Formed in the Presence of Neutrophils." Investigative Ophthalmology & Visual Science 52.5 (2011): 2844-850. Print. PMID: 21245396.

 

Inventors
J.A. Nick, MD, T.S. Walker, G.S. Worthen, MD, Quinn Parks, PhD

 

Patents
U.S. Patents #8,753,662 and #8,901,167. International Patent Application #WO2006/017816. Additional patents pending.

 

Licensing Status
This technology is available for licensing.

 

For Further Information, Contact:
Emmanuel Hilaire, PhD
Manager
Technology Transfer Office
National Jewish Health
1400 Jackson Street, Room M206b
Denver, CO 80206
Voice: 303.398.1262
Fax: 303.270.2352
HilaireE@njhealth.org

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