Dokument

Summary:
In the incessant effort of living and propagating, bacterial cells cope with environmental stress via the release of second messengers and/or alarmones that allow them to adapt swiftly. Such molecules are nucleotidebased and can be promptly generated when stress stimuli occur. According to the cellular concentration of stress mediators, specific molecular targets would be activated to modulate vital processes for bacterial survival and proliferation. As soon as the stress is over, cells would repristinate the initial concentration of the stress-coping mediators with deputed enzymes. Overall, the aforementioned mechanisms fall in the definition of Bacterial Stress Response (BSF). The aim of the present doctoral thesis is to illustrate and discuss three published scientific articles that contributed to the understanding of the BSF in bacterial cells and the role of the stress mediators 5',5'''-diadenosine tetraphosphate (Ap4A) and ppGpp and pppGpp (collectively (p)ppGpp). The Publication #1 described how Ap4A could restrict the activity of the essential enzyme inosine monophosphate dehydrogenase (IMPDH) in Bacillus subtilis in order to reprogram the levels of purine nucleotides during heat shock. The present publication proposed IMPDH as the first physiologically confirmed target of Ap4A in prokaryotes and characterized the molecular mechanisms of how Ap4A inhibits IMPDH. The biological relevance of the interaction Ap4A-IMPDH was further analyzed and proven with in vivo experiments.

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