In order to deal with various environmental conditions, most living organisms adapt and respond to environmental cues through nucleotide-based second-messenger signaling. Such signals regulate various endogenous factors required for environmental adaptation. In bacteria, there are five kinds of nucleotide-based second messengers, one of which is cyclic di-guanosine monophosphate (c-di-GMP). The molecule is known to regulate many cellular functions including growth, motility, biofilm formation, and virulence. Various environmental cues cause changes in the intracellular concentration of c-di-GMP, depending on the activity of specific c-di-GMP synthases and hydrolases in cells. In this review, we provide insights into nucleotide signaling in bacteria, emphasizing its impact on basic metabolism, its association with other signaling mechanisms, and its role in regulating the virulence of a wide range of bacteria. Moreover, we discuss recent studies suggesting a role for the implicated signaling molecules in bacterial persistence and antibiotic resistance.

Turmeric is known for its ability to enhance immunity via anti-inflammatory and anti-oxidant effects. Salmonella enterica species contain a large number of pathogenic serotypes that are adapted to a broad range of vertebrate hosts. Our previous study revealed that bioprocessed polysaccharides from the liquid culture Lentinus edodes fungal mycelia containing turmeric (BPP-turmeric) is able to alter chicken macrophage responses and increases chick survival against Salmonella enterica infection. In this study, we examined the immunomodulatory effects of BPP-turmeric on the porcine macrophage 3D4/31 cell line infected with Salmonella enterica subsp. enterica serovar Choleraesuis (S. Choleraesuis) or S. Enteritidis. Our experimental analyses demonstrated that BPP-turmeric (i) does not alter phagocytic and killing activity of 3D4/31 against either Salmonella serotypes, but that it (ii) represses mRNA transcription of interleukin (IL)-6, IL-8, and tumor necrosis factor α in response to Salmonella infection. Collectively, these results imply that BPP-turmeric has an immunomodulatory effect that represses pro-inflammatory cytokine expression in porcine macrophages, suggesting that it may protect swine from salmonellosis via controlling Salmonella-induced hyperinflammation.

Bioenergetics has been defined as the biology of energy transformations and energy exchanges within and between living organisms and their environment; this field now includes the concept of bioenergetic medicine, e.g., therapeutic approaches involving biophotons. QELBY® powder is a patented quantum energy-radiating material (patent No. 10-1172018), to be precise, a biologically active silicon dioxide-containing mineral powder that radiates reductive energy in infrared wavelength. In this study, we examined possible biological effects of indirect contact with QELBY® powder on various mammalian cell lines derived from macrophagic (MØ) and nonmacrophagic cells, including Raw 264.7 (mouse-derived MØ cell line), HD11 (chicken-derived MØ cell line), and HeLa (human cervical cancer cell line). Our comparison among the cells with and without indirect contact with QELBY® powder showed that this indirect contact significantly (i) increased the mitochondrial membrane potential (up to 1.36-fold) regardless of the cell type (p < 0.05), (ii) decreased the intracellular concentration of ATP in HeLa cells but not in the MØ-derived cells (p < 0.05), and (iii) protected DNA from damage during oxidative stress according to a standard comet assay (single-cell alkaline gel electrophoresis). Taken together, these results imply that indirect contact with QELBY® powder can make cells more metabolically active by increasing the mitochondrial membrane potential and by alleviating DNA damage caused by oxidative stress.

Shiga toxins (Stxs), some of the most important virulence factors in enterohemorrhagic Escherichia coli (EHEC) O157:H7, are known to be induced and released by various environmental cues, such as DNA damage responses and stress-inducing chemicals. In order to investigate the possible effects of growth media on Stxs expression, we analyzed the growth kinetics and expression of Stxs (Stx1 and 2) in cells grown in Luria-Bertani (LB) and E. coli (EC) media, which are widely used for EHEC O157:H7. Through direct plating and quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR), it was revealed that, when EHEC O157:H7 was grown in EC medium, the total bacterial count was reduced significantly and the stx1 transcription was greatly increased during the stationary growth phase than that in LB. Here we report that bile salts and lactose, which are the two only components in EC medium that are absent in LB, function as negative and positive regulatory signals, respectively, for the transcription of both stx1 and stx2. Indeed, stx transcription was significantly increased (~5.7 and ~21.8 fold for stx1 and stx2, respectively; p < 0.05) in an EC medium lacking bile salts when compared to the normal EC. In contrast, EHEC O157:H7 grown in an EC medium lacking lactose did significantly decrease these transcriptions (~93.5 and ~4.3 fold for stx1 and stx2, respectively; p < 0.05). Consistently, stx transcription was drastically increased in an LB medium supplemented with lactose, implying that lactose might be an environmental trigger for the expression of Stxs.