Persisters are microbial cells which entered a dormant, slow-growing state that renders them able to survive antibiotics. These cells are the major cause of chronic infections after medical interventions as they often constitute biofilms, aggregates of microorganisms growing on the surface of medical devices such as catheters or prostheses.
B. P. Conlon, Northeastern University, Boston, MA, USA, and colleagues report a new way to fight persisters. The researchers demonstrated that the antibiotic ADEP4 (pictured), a potent acyldepsipeptide derivative, kills drug-tolerant persistent cells by activating a protein known as ClpP. Since this molecule is a nonspecific protease, its activation by ADEP4 leads to the degradation of more than 400 proteins, thereby inducing persistent cells to self-digest. As a consequence, when combined to the antibiotic rifampicin, ADEP4 completely eradicated biofilms formed by the highly pathogenic bacteria Staphylococcus aureus.
ADEP4 may thus constitute an invaluable tool to treat chronic infections.
- Activated ClpP kills persisters and eradicates a chronic biofilm infection,
B. P. Conlon, E. S. Nakayasu, L. E. Fleck, M. D. LaFleur, V. M. Isabella, K. Coleman, S. N. Leonard, R. D. Smith, J. N. Adkins, K. Lewis,
Nature 2013, 503, 365–370.