Abstract
Stress and starvation causes bacterial cells to activate the stringent response. This results in down-regulation of energy-requiring processes related to growth, as well as an upregulation of genes associated with survival and stress responses. Guanosine tetra- and pentaphosphates (collectively referred to as (p)ppGpp) are critical for this process. In Gram-positive bacteria, a main function of (p)ppGpp is to limit cellular levels of GTP, one consequence of which is reduced transcription of genes that require GTP as the initiating nucleotide, such as rRNA genes. In Streptomycetes, the stringent response is also linked to complex morphological differentiation and to production of secondary metabolites, including antibiotics. These processes are also influenced by the second messenger c-di-GMP. Since GTP is a substrate for both (p)ppGpp and c-di-GMP, a finely tuned regulation of cellular GTP levels is required to ensure adequate synthesis of these guanosine derivatives. Here, we discuss mechanisms that operate to control guanosine metabolism and how they impinge on the production of antibiotics in Streptomyces species.
Highlights
IntroductionEither in the environment or when infecting a host
Bacteria experience constant challenges, either in the environment or when infecting a host
We propose that regulation of purine metabolism and GTP homeostasis in Streptomycetes is distinct from that reported in B. subtilis and that these processes need to be carefully managed to maintain the optimal synthesis of guanosine nucleotide second messengers
Summary
Either in the environment or when infecting a host They utilize various mechanisms to survive such stresses, which may include changes in temperature, pH, or oxygen content as well as limited access to carbon or nitrogen sources. A stress response that is mobilized to deal with events such as nutrient limitation is the stringent response The purpose of this response is to focus cellular resources on survival, as opposed to growth [1]. In multicellular Actinomycetes, such as Streptomyces spp., c-di-GMP is involved in controlling developmental processes [3] These signaling molecules require the presence of purines to sustain their synthesis under conditions of stress and starvation, circumstances under which the bacterial cell must conserve essential nutrients. We discuss how purine metabolism affects antibiotic production, with an emphasis on the stringent response
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