A new web app eNTRyway speeds the discovery of drugs to kill Gram-negative bacteria by quickly evaluating potential drugs ability to accumulate in these bacterial cell. Entryway calculates physiochemical properties of molecules and compares 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 different 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 so far 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 a variety of different ways. The newly created drug, known as Debio-1452-NH3, interferes with fatty acid synthesis in bacterial – but not mammalian – cells.