Cellular and molecular bases of the regulation of bacterial persistence by (p)ppGpp synthetases / hydrolase

bacteriology • persistence • structural biology

Abel Garcia-Pino is professor at the Université libre de Bruxelles. He manages the Structural and Biophysical Biology lab and studies the molecular bases for the survival of bacteria.

Many of the difficulties associated with treating infectious diseases with antibiotics are not caused by an intrinsic genetic resistance, but rather the presence of quiescent cells called “persisters”. Persistence is a physiological restart mechanism that allows certain cells in an isogenic bacterial population to resist a wide variety of stresses. The ppGpp (guanosine tetraphosphate) molecule is one primary regulator of the stringent response, as well as the effector that allows the shift towards persistence. Understanding the mechanisms that regulate ppGpp synthesis is still one of the most significant problems for modern microbiology.

This project aims to understand the key stages in the molecular mechanisms behind ppGpp synthesis and hydrolysis in various species of bacteria, by studying the regulatory interactions between ReIA and SpoT proteins, which control ppGpp levels during persistence. This work will make it possible to develop ReIA/SpoT inhibitors that have the potential to inhibit persistence.

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