bis(3--5-)-cyclic-diguanylic-acid and Inflammation

Iron is necessary for the survival of almost all aerobic organisms. In the mammalian host, iron is a required cofactor for the assembly of functional iron-sulfur (Fe-S) cluster proteins, heme-binding proteins and ribonucleotide reductases that regulate various functions, including heme synthesis, oxygen transport and DNA synthesis. However, the bioavailability of iron is low due to its insolubility under aerobic conditions. Moreover, the host coordinates a nutritional immune response to restrict the accessibility of iron against potential pathogens. To counter nutritional immunity, most commensal and pathogenic bacteria synthesize and secrete small iron chelators termed siderophores. Siderophores have potent affinity for iron, which allows them to seize the essential metal from the host iron-binding proteins. To safeguard against iron thievery, the host relies upon the innate immune protein, lipocalin 2 (Lcn2), which could sequester catecholate-type siderophores and thus impede bacterial growth. However, certain bacteria are capable of outmaneuvering the host by either producing "stealth" siderophores or by expressing competitive antagonists that bind Lcn2 in lieu of siderophores. In this review, we summarize the mechanisms underlying the complex iron tug-of-war between host and bacteria with an emphasis on how host innate immunity responds to siderophores.

Topics: Cyclic GMP; Ferrous Compounds; Host Microbial Interactions; Humans; Immunity, Innate; Inflammation; Iron; Lipocalin-2; Neutrophils; Peptides; Reactive Oxygen Species; Siderophores

Inflammatory bowel disease (IBD) symbolizes a group of intestinal disorders in which prolonged inflammation occur in the digestive tract (esophagus, large intestine, small intestine mouth, stomach). Both genetic and environmental factors (infections, stress, diet) are involved in the development of IBD. As we know that bacteria are found in the intestinal mucosa of human and clinical observations revealed bacterial biofilms associated with patients of IBD. Various factors and microbes are found to play an essential role in biofilm formation and mucosal colonization during IBD. Biofilm formation in the digestive tract is dependent on an extracellular matrix synthesized by the bacteria and it has an adverse effect on the immune response of the host. There is no satisfactory and safe treatment option for IBD. Therefore, the current research aims to disrupt biofilm in IBD and concentrates predominantly on improving the drug. Here, we review the literature on bacterial biofilm and IBD to gather new knowledge on the current understanding of biofilm formation in IBD, host immune deregulation and dysbiosis in IBD, molecular mechanism, bacteria involved in biofilm formation, current and future regimen. It is urgently required to plan new ways to control and eradicate bacteria in biofilms that will open up novel diagnostic and therapeutic avenues for IBD. This article includes the mechanism of signaling molecules with respect to the biofilm-related genes as well as the diagnostic methods and new technologies involved in the treatment of IBD.

Topics: Anti-Inflammatory Agents; Bacteria; Biofilms; Cyclic GMP; Dysbiosis; Gastrointestinal Microbiome; Gastrointestinal Tract; Humans; Immunosuppressive Agents; Inflammation; Inflammatory Bowel Diseases; Intestinal Mucosa; Intestines; Quorum Sensing; Stomach

Curli, a major component of the bacterial biofilms in the intestinal tract, activates pattern recognition receptors and triggers joint inflammation after infection with Salmonella enterica serovar Typhimurium. The factors that allow

Topics: Bacterial Proteins; Biofilms; Cues; Cyclic GMP; Flagella; Gene Expression Regulation, Bacterial; Humans; Inflammation; Nitrates; Salmonella enterica; Salmonella typhimurium; Serogroup

Topics: Alternaria; Alternariosis; Animals; Cyclic GMP; Cytokines; Immunity, Innate; Inflammation; Lung; Membrane Proteins; Mice; Mice, Knockout; Pneumonia; Signal Transduction

Bacteria that colonize animals must overcome, or coexist, with the reactive oxygen species products of inflammation, a front-line defense of innate immunity. Among these is the neutrophilic oxidant bleach, hypochlorous acid (HOCl), a potent antimicrobial that plays a primary role in killing bacteria through nonspecific oxidation of proteins, lipids, and DNA. Here, we report that in response to increasing HOCl levels, Escherichia coli regulates biofilm production via activation of the diguanylate cyclase DgcZ. We identify the mechanism of DgcZ sensing of HOCl to be direct oxidation of its regulatory chemoreceptor zinc-binding (CZB) domain. Dissection of CZB signal transduction reveals that oxidation of the conserved zinc-binding cysteine controls CZB Zn

Topics: Bacteria; Bacterial Adhesion; Biofilms; Cyclic GMP; Escherichia coli; Escherichia coli Proteins; Gene Expression Regulation, Bacterial; Genome, Bacterial; Hypochlorous Acid; Inflammation; Signal Transduction

The synthesis of mono- and bisphosphorothioate analogues of 3',5'-cyclic diguanylic acid (cdiGMP) via the modified H-phosphonate chemistry is reported. The immunostimulatory properties of these analogues were compared with those of cdiGMP.

Topics: Bronchi; Chemistry, Pharmaceutical; Chromatography, High Pressure Liquid; Cyclic GMP; Dose-Response Relationship, Drug; Drug Design; Humans; Immune System; Inflammation; Models, Chemical; Neutrophils; Organophosphonates; Phosphates; Vaccines