Superantibiotic EVG7 leaves good bacteria unharmed

Even before the article was published in Science Translational Medicine, professor of biological chemistry Nathaniel Martin had already presented some of the findings to Wiep Klaas Smits, a colleague at Leiden University Medical Centre. ‘Wiep Klaas and his group are experts in the field of C. diff‘, says Martin, ‘and he offered some patient-derived C. diff samples to test EVG7 on.’

As expected, the super-antibiotic proved highly effective, given that C. diff is a gram-positive bacterium. ‘We consistently observed that EVG7 was ten times more potent against C. diff than the clinically used gold standard, vancomycin’, Martin explains. Whilst vancomycin does suppress the growth of C. diff, it also eliminates the so-called commensal bacteria that are beneficial to the gut. ‘In the absence of protective commensal bacteria, even a small quantity of C. diff spores can lead to a relapse infection that may be even worse than the original infection.’ This relapse or recurrence of infection is something many patients experience after becoming infected with this bacterium.

Curative effect

Martin and his team then evaluated EVG7 in a mouse model of C. diff infection, developed by Casey Theriot of North Carolina State University, and it ‘worked exceptionally well’. In the model, mice treated with vancomycin typically relapse after two weeks, but this was not the case with EVG7; it appears to have a lasting effect.

This observation is particularly exciting, Martin explains: ‘Patients treated with vancomycin often have to undergo multiple courses of antibiotics due to recurring infections, which is associated with higher mortality rates. The finding that EVG7 produces a curative effect after a single course of treatment, with no signs of relapse, is very encouraging.’

But why is EVG7 more active against Clostridium than against the beneficial commensal bacteria? ‘That is a good question, and we still don’t have a definitive answer’, Martin acknowledges. ‘It may be that EVG7, owing to its structural modification, binds more effectively to C. difficile than to commensals, but confirming this will require further mechanistic research.’

Broad potential

Martin hopes that this article will generate interest in EVG7 within the wider community. ‘At present, we are busy conducting a number of pre-clinical studies. Together with Elma Mons, the postdoc leading the project in the Martin Group, and Coen van Hasselt from the LACDR, we have received a NACTAR grant from NWO to investigate how the compound can be dosed most effectively, which is crucial for setting up human trials.’

Alongside several other studies into biodistribution and toxicology, Martin and his colleagues are steadily building a robust dossier on the efficacy and safety of EVG7. Whilst the first clinical indication for their antibiotic is likely to be acute bacterial skin and skin structure infections – ‘ABSSSIs, a common first indication for new antibiotics’ – the current study demonstrates its broader potential. ‘If EVG7 is approved for an indication such as ABSSSIs, that will pave the way for evaluation of the compound in the treatment of other types of infection. Our recently published studies demonstrating the efficacy of EVG7 in treating C. diff may therefore provide a rationale for using EVG7 in the future to treat such infections’, says Martin. ‘All in all, we are putting together a compelling list of all the advantages of EVG7 over vancomycin.’

Mons, E. et al. (2025) Nat. Commun. 16, DOI: 10.1038/s41467-025-64067-w