The rapid emergence of multidrug-resistant bacteria, or superbugs, is a critical global health issue. While there is a compelling need for new antibiotics, their development has slowed dramatically in recent years. The last Schematic of the screening methodology. Source: University of Colorado BoulderSchematic of the screening methodology. Source: University of Colorado Bouldertime a new class of antibiotics was marketed was in 1984, according to the Pew Charitable Trust.

University of Colorado Boulder researchers are advancing a therapeutic alternative to new drug development: make existing antibiotics more powerful. New molecules with antimicrobial properties are identified by SAFIRE (screen for anti-infectives using fluorescence microscopy of intracellular enterobacteriaceae). The screening platform detects compounds active against Gram-negative bacteria within the context of host cells by use of fluorescence microscopy and automated image analysis. These compounds could be used to increase pathogen sensitivity to existing antibiotics.

Of 14,400 potential candidates screened, SAFIRE has revealed at least three with strong potential to rejuvenate the therapeutic power of available antibiotics. These compounds do not inactivate the bacteria itself, but instead penetrate the pathogen and shut down cellular machines called efflux pumps, which bacteria use to protect themselves from both antibiotic medications and the body’s own immune-boosting proteins.

The researchers are collaborating with Boulder-based pharmaceutical start-up Crestone Inc. to help refine the compounds, with plans to start animal trials in the near-term.

The research is published in PLOS Pathogens.

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