Abstract

The treatment of bacterial infections with antibiotics is significantly complicated because of the adaptive mechanisms employed by bacteria. Chronic and recurrent infections are often linked to bacterial persis-tence, biofilm formation, and antibiotic tolerance. These processes result in reduced metabolic activity, rendering bacteria insensitive to conventional antibiotics that primarily target actively growing cells. The stringent re-sponse, regulated by (p)ppGpp alarmone molecules, serves as a stress adaptation mechanism. It is conserved across numerous bacterial species and plays an important role in long-term survival under nutrient-depleted con-ditions. (p)ppGpp alarmones also play a significant role in bacterial persistence and the formation of biofilms. The pursuit of novel antibacterial agents that specifically target (p)ppGpp synthesis, thereby inhibiting the strin-gent response, presents a promising strategy in the battle against bacterial infections. In this context, alarmone synthetase inhibitors emerge as promising candidates for clinical application, as they have demonstrated their effectiveness in suppressing bacterial survival mechanisms, inhibiting biofilm formation, and reducing antibiotic tolerance and bacterial persistence.

Full Text
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