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Post-Translational Regulation of C-Reactive Protein Secretion
Published in Andrzej Mackiewicz, Irving Kushner, Heinz Baumann, Acute Phase Proteins, 2020
Stephen S. Macintyre, Patricia A. Kalonick
CRP has been a particularly useful protein in illuminating the mechanisms regulating the intracellular transport of secretory proteins. In the remainder of this chapter, we review evidence which demonstrates that the secretion of CRP becomes more efficient during the acute phase response, and present new data on the molecular mechanisms which regulate the intracellular sorting of CRP under differing physiologic conditions.
Pili and Hosts
Published in Paul Pumpens, Single-Stranded RNA Phages, 2020
Furthermore, cyclic AMP and its receptor protein appeared as being required for the expression of tra operon in E. coli Hfr cells: a number of cya and crp mutants demonstrated inability to adsorb the phages MS2 and Qβ, but cAMP supplementation suppressed this defect in cya but not in crp mutants (Kumar and Srivastava 1983). This inability was caused by the simple fact that the cya and crp mutants did not produce F pili in normal amounts.
Site-Selective cAMP Analogs in the Arrest of Cancer Cell Growth
Published in Robert I. Glazer, Developments in Cancer Chemotherapy, 2019
By using site-selective analogs in vivo, the cellular cyclic nucleotide effector mechanisms involved in cAMP-mediated response in vivo can be studied because (1) a new test is available to establish whether or not the cAMP receptor protein is the mediator of the response; (2) the analog binding to Site 1 and 2 is cooperative, and therefore the analog sensitivity toward synergism for binding to the cAMP receptor protein in intact cells can be measured; (3) if the analog combinations would demonstrate synergism, lower total analog concentrations could be used to achieve the same cellular response obtained by using a single analog; and (4) one of two protein kinase isozymes present in intact cells can be selectively modulated to correlate the analog effect with protein kinase isozyme.
YjbH mediates the oxidative stress response and infection by regulating SpxA1 and the phosphoenolpyruvate-carbohydrate phosphotransferase system (PTS) in Listeria monocytogenes
Published in Gut Microbes, 2021
Changyong Cheng, Xiao Han, Jiali Xu, Jing Sun, Kang Li, Yue Han, Mianmian Chen, Houhui Song
Bacteria maintain the cytosolic redox status largely by using redox-regulating thiol molecules such as glutathione and the dicysteine proteins thioredoxin and glutaredoxin.13 At the expense of NADPH, glutathione is maintained in a reduced state by glutathione reductase, and thioredoxin is kept reduced by thioredoxin reductase.14 Many Gram-positive bacteria mainly employ low-molecular-weight thiols, thioredoxin, and alternative thioredoxin-based enzymes as antioxidant systems.15,16 The thioredoxin family contains a common structural fold (the Trx domain) and is involved in cellular defense against oxidative stress caused by reactive oxygen species (ROS).17 Thioredoxin is the major cellular disulfide reductase in cells, which can provide a highly reducing environment and then function as an effector to facilitate correct oxidative protein folding. In L. monocytogenes, PrfA, a cAMP receptor protein (Crp) family transcriptional regulator that is essential for virulence gene expression and pathogenesis,18 is exclusively activated in the cytosol of host cells. The glutathione generated by bacteria or derived from host cells is the essential small-molecule cofactor of PrfA. Glutathione allosterically binds to PrfA, thereby increasing its activity regarding inducing target genes.19,20
Targeting the gut microbial metabolic pathway with small molecules decreases uremic toxin production
Published in Gut Microbes, 2020
Yingyi Wang, Jianping Li, Chenkai Chen, Jingbo Lu, Jingao Yu, Xuejun Xu, Yin Peng, Sen Zhang, Shu Jiang, Jianming Guo, Jinao Duan
The second messenger cyclic adenosine monophosphate (cAMP) can amplify and transduce signals in bacteria.34 In E. coli, the cAMP receptor protein (CRP) is activated after binding with cAMP, the CRP-cAMP complex regulates the transcription of TnaA and TnaB.35 Exogenous cAMP (5 mM) promotes tryptophan consumption and indole production, which is likely due to increased TnaA/B gene expression and TnaA/B protein synthesis (Figure 2d). However, in the presence of cAMP, ISO still significantly inhibits tryptophan consumption and indole synthesis, thereby suggesting that ISO does not directly act on TnaA gene expression and, thus, TnaA protein synthesis in E. coli.
Novel targets and inhibitors of the Mycobacterium tuberculosis cytochrome bd oxidase to foster anti-tuberculosis drug discovery
Published in Expert Opinion on Drug Discovery, 2023
Amaravadhi Harikishore, Vikneswaran Mathiyazakan, Kevin Pethe, Gerhard Grüber
During infection, mycobacteria inhabit a wide range of intracellular (macrophages, epithelioid cells) and extracellular environments like the central caseum of necrotic granulomas. In necrotic granulomas, the pathogen is found largely in the caseum, with smaller numbers of Mtb bacilli living intracellularly within the macrophage-rich regions surrounding the caseum [24]. The prevailing hypothesis is that the intracaseum Mtb bacilli contributes to the persistent nature of TB infection in humans and the need for prolonged chemotherapeutic intervention. The avascular and necrotic nature of the caseous core generates hypoxic conditions which, in turn, induce nonreplicating growth and persistence in Mtb [25–28]. Mycobacteria have adapted to survive in hypoxia conditions [29,30], by elevating the expression of the cydAB genes, which encode for cyt-bd, a class of respiratory quinol: O₂ oxidoreductases known for possessing high affinity toward oxygen [17]. Several lines of evidence indicate that hypoxia induce cAMP receptor protein (CRP1/2) signaling, which positively regulates cyt-bd oxidase expression [16,31,32]. In aerobic conditions, CRP signaling negatively regulates cydA expression and the deletion mutant ΔCRP (Rv3676) enhances cydA expression by 2.5-fold in Mtb. The expression levels of cyd genes are upregulated during chronic TB infection in mouse lungs. In addition, the sustained release of necrotizing foamy macrophages in caseum is thought to increase oxygen- and nitrogen-reactive species, also known to induce nonreplicating persistence [33,34]. The high oxygen affinity of cyt-bd may allow the enzyme to act as efficient electron sink and to regulate the amount of oxygen species the pathogen is exposed to. Furthermore, transcriptome profiling has shown an upregulation of the cydAB genes in the presence of nitrogen-reactive species [16]. All these findings underline cyt-bd’s importance for metabolic adaptation in Mtb during infection and the dormant state, enabling the pathogen to deal with various and rapidly changing environmental challenges.