Guanosine 5'-diphosphate 3'-diphosphate (ppGpp) (ppGpp)

Guanosine tetraphosphate (ppGpp) is a signaling nucleotide, commonly known as an 'alarmone,' that plays a central role in the bacterial stringent response [1][2]. It is synthesized by enzymes of the RelA/SpoT Homolog (RSH) family in response to environmental stresses such as amino acid starvation, fatty acid limitation, or heat shock [3]. Elevated levels of ppGpp trigger a global shift in bacterial metabolism, redirecting resources from growth and proliferation toward survival and stress resistance by modulating RNA polymerase activity [4]. This molecule is a key regulator of bacterial virulence, biofilm formation, and the development of antibiotic persistence, which allows bacteria to survive lethal doses of antibiotics without acquiring resistance mutations [5]. Because the ppGpp signaling pathway is absent in mammals, it represents a promising target for the development of narrow-spectrum or adjuvant antimicrobial agents [6]. Current therapeutic strategies focus on inhibiting the enzymes responsible for ppGpp synthesis, such as RelA, to disrupt the bacterial ability to adapt to host-induced stress and enhance the efficacy of existing antibiotics [7].

Other names

ppGppMagic Spot IGuanosine-3',5'-bis(diphosphate)Guanosine tetraphosphateGuanosine-3'-diphosphate-5'-diphosphate

Inhibition of (p)ppGpp synthetases (RelA/SpoT) to prevent the stringent response and reduce bacterial virulence and persistence.