Rational Design of Aminoglycoside-Based Antibiotics

Tech ID: 30020 / UC Case 2014-732-0

Summary

UCLA researchers in the Department of Bioengineering have designed a novel class of antibiotics that are effective against resistant bacterial infections.

Background

The global antibiotics market is projected to reach $44.7 billion by 2020 growing at a CAGR of 2%. Most antibiotics are aminoglycoside or beta-lactam molecules and are used for treating chronic microbial infections. Aminoglycosides are broad-spectrum antibiotics that are effective against gram-negative and aerobic microbes. However, most bacterial strains develop resistance over time. The main cause of resistance is dormant cells, called persistent cells, that are not penetrated by aminoglycosides. Additionally, aminoglycosides do not target gram-positive and anaerobic microbes. Targeting persistent cells and increasing the potency of aminoglycosides against gram-positive bacteria will help clear recurrent and antibiotic-resistant infections.

Innovation

UCLA researchers have developed a novel approach to increase the potency of aminoglycosides. They have determined a set of chemical rules to modify aminoglycosides such that they can target the persistent cells. Their simple approach can be used to conjugate any antibiotic and is thus applicable for different antibiotics. They designed and synthesized a novel antibiotic called Pentobra which kills dormant cells, unlike generic aminoglycosides, and is effective against both gram-positive and gram-negative bacteria. Pentrobra also shows 5-7 fold higher efficacy against acne-causing strains and is safe for human cells in vitro.

Applications

  • Acne treatment 
  • Treatment of Tuberculosis, Pneumonia, Typhoid and other bacterial infections 
  • Treatment of MRSA and Staphylococcus strains 
  • Treatment of foodborne illnesses

Advantages

  • Deterministic and rational approach for design 
  • Synergistic approach to clear dividing and persistent cells 
  • Effective against both gram-positive and gram-negative bacteria

State Of Development

Design rules established and novel antibiotic developed (Pentobra). Antibiotic extensively tested in bacterial killing assays with a range of different bacteria and clinically isolated strains.

Related Materials

  • Schmidt NW, Agak GW, Deshayes S, Yu Y, Blacker A, Champer J, Xian W, Kasko AM, Kim J, Wong GCL. “Pentobra: A Potent Antibiotic with Multiple Layers of Selective Antimicrobial Mechanisms against Propionibacterium Acnes” J. Invest. Dermatol. 2015
  • Schmidt NW, Deshayes S, Hawker S, Blacker A, Kasko AM, Wong GC. “Engineering persister-specific antibiotics with synergistic antimicrobial functions.” ACS Nano. 2014

Patent Status

Country Type Number Dated Case
United States Of America Published Application 20170348337 12/07/2017 2014-732
European Patent Office Published Application WO2016025627 02/18/2016 2014-732
 

Contact

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Inventors

  • Wong, Gerard CL.

Other Information

Keywords

Antibiotics, Persistent cells, Bactericidal, Chronic infections, Bacteria, Infections, Acne

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