All bacteria, including major pathogens such as TB, MRSA, Salmonella, etc, form persistent forms with low frequency that can survive antibiotic treatment. In healthy individuals, the immune system eradicates these rare bacteria. However, in debilitated or elderly individuals, such surviving bacteria can generate the basis for chronic or relapsing infections.
We discovered that the intracellular regulatory molecule, (p)ppGpp, present in almost all bacteria, is the master regulator of the persistence phenomenon. The cellular level of (p)ppGpp is high in low fractions of growing bacterial populations and these bacteria are resistant to multiple antibiotics and thus survive during chemotherapy.
In the DNRF and Novo Nordisk Foundation Centre for Bacterial Stress Response and Persistence (BASP) at the Dept. of Biology, University of Copenhagen, we will study how bacteria control their levels of (p)ppGpp and how it allows them to survive many different types of environmental stresses, including antibiotics.