UCLA researchers in the California NanoSystems Institute have discovered novel and potent therapeutic agents against Burkholderia bacteria, E. Coli and pseudomonas bacterial infections through cell-based phenotypic screening that are more effective than existing treatments.
BACKGROUND:
Burkholderia pseudomallei (Bp) and Burkholderia mallei (Bm) cause Melioidosis and Glanders, respectively, which are lethal infections that plague regions such as Asia, Africa and Northern Australia. These bacteria are classified as Tier-1 select agents by the CDC and have been historically utilized in bio-warfare and bio-terrorism. The HHS has identified these diseases as top priorities for development of medical countermeasures. Currently, there are limited therapeutics available for these pathogens, such as antibiotics ceftazidime and cefepime. And treatment plans involve intravenous and oral dosages that last for months.
INNOVATION:
Researchers have made a novel discovery through cell-based phenotypic screening that a novel fluoroquinolone analog, named burkfloxacin (BFX), and flucytosine (5-FC), an FDA- approved antifungal drug, have potent activities against Bp and Bm. BFX effectively inhibits growth of intracellular Burkholderia and 5-FC inhibits Burkholderia-mediated membrane fusion and intercellular spread. Treatments with BFX and 5-FC were shown to be significantly more effective than ceftazidime in a fulminant murine melioidosis model. P. aeruginosa and E. coli are susceptible to BFX as well. BFX has similar in vitro activity against these organisms as Cip [ciprofloxacin] and levofloxacin.
POTENTIAL APPLICATIONS:
ADVANTAGES