cyclic-gmp and 2-heptyl-3-hydroxy-4-quinolone

Bacteria use diverse small molecules for extra- and intracellular signaling. They scan small-molecule mixtures to access information about both their extracellular environment and their intracellular physiological status, and based on this information, they continuously interpret their circumstances and react rapidly to changes. Bacteria must integrate extra- and intracellular signaling information to mount appropriate responses to changes in their environment. We review recent research into two fundamental bacterial small-molecule signaling pathways: extracellular quorum-sensing signaling and intracellular cyclic dinucleotide signaling. We suggest how these two pathways may converge to control complex processes including multicellularity, biofilm formation, and virulence. We also outline new questions that have arisen from recent studies in these fields.

Topics: 4-Butyrolactone; Bacterial Physiological Phenomena; Bacterial Proteins; Biofilms; Cyclic GMP; Escherichia coli Proteins; Gene Expression Regulation, Bacterial; Genes, Bacterial; Homoserine; Lactones; Models, Biological; Oligopeptides; Phosphoric Diester Hydrolases; Phosphorus-Oxygen Lyases; Purine Nucleotides; Quinolones; Second Messenger Systems; Signal Transduction; Virulence

Bitter taste receptors (T2Rs) are GPCRs involved in detection of bitter compounds by type 2 taste cells of the tongue, but are also expressed in other tissues throughout the body, including the airways, gastrointestinal tract, and brain. These T2Rs can be activated by several bacterial products and regulate innate immune responses in several cell types. Expression of T2Rs has been demonstrated in immune cells like neutrophils; however, the molecular details of their signaling are unknown. We examined mechanisms of T2R signaling in primary human monocyte-derived unprimed (M0) macrophages (M[Formula: see text]s) using live cell imaging techniques. Known bitter compounds and bacterial T2R agonists activated low-level calcium signals through a pertussis toxin (PTX)-sensitive, phospholipase C-dependent, and inositol trisphosphate receptor-dependent calcium release pathway. These calcium signals activated low-level nitric oxide (NO) production via endothelial and neuronal NO synthase (NOS) isoforms. NO production increased cellular cGMP and enhanced acute phagocytosis ~ threefold over 30-60 min via protein kinase G. In parallel with calcium elevation, T2R activation lowered cAMP, also through a PTX-sensitive pathway. The cAMP decrease also contributed to enhanced phagocytosis. Moreover, a co-culture model with airway epithelial cells demonstrated that NO produced by epithelial cells can also acutely enhance M[Formula: see text] phagocytosis. Together, these data define M[Formula: see text] T2R signal transduction and support an immune recognition role for T2Rs in M[Formula: see text] cell physiology.

Topics: Calcium; Cell Communication; Cells, Cultured; Coculture Techniques; Cyclic GMP; Epithelial Cells; Humans; Macrophages; Monocytes; Nitric Oxide; Nitric Oxide Synthase Type III; Pertussis Toxin; Phagocytosis; Physostigmine; Quinolones; Receptors, G-Protein-Coupled; Signal Transduction