A new web app, eNTRyway (Link), speeds the discovery of drugs to kill Gram-negative bacteria by quickly evaluating potential drugs’ ability to accumulate in these bacterial cells. Entryway calculates the physiochemical properties of molecules and compares them to a training set of compounds. The tool also offers insights into discrete chemical changes that can convert drugs that kill other bacteria into drugs to fight Gram-negative infections.
The team proved the system works by modifying a Gram-positive drug and testing it against three Gram-negative bacterial culprits in mouse sepsis. The drug was successful against each.
The researchers report their findings in the journal Nature Microbiology.
Researchers have identified more than 60 antibiotics that are effective only against Gram-positive bacteria but can be converted into drugs to fight Gram-negative infections. These compounds kill bacteria in various ways. The newly created drug, known as Debio-1452-NH3, interferes with fatty acid synthesis in bacterial—but not mammalian—cells.
Reference
Parker, E.N., Drown, B.S., Geddes, E.J. et al. Implementation of permeation rules leads to a FabI inhibitor with activity against Gram-negative pathogens. Nat Microbiol 5, 67–75 (2020). https://doi.org/10.1038/s41564-019-0604-5
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