Project description:Helicobacter pylori (H. pylori) colonize the stomach epithelium of half the world's population and are responsible for a variety of digestive diseases and even stomach cancer. The protection against H. pylori infection depends primarily on the antigen-mediated mucosal and T cell responses. We hypothesized that lipopeptide vaccines obtained by covalently conjugation of Pam2Cys with strong mucosal adjuvant activity to the immunodominant epitope from protective antigens could induce protective responses against H. pylori infection. In this study, the synthetic lipopeptide vaccines, Hp4 (Pam2Cys modified UreB T cell epitope) and Hp10 (Pam2Cys modified CagA T/B cell combined epitope), induced the BMDCs maturation in vitro by activating a variety of pattern recognition receptors such as TLR, NLR and RLR. In addition, lipopeptide vaccines stimulated BMDCs to secret cytokines that have the potential to modulate T cell activation and differentiation. Although intranasal immunization with Hp4 or Hp10 elicited robust epitope-specific T cell responses in mice, only Hp10 conferred protection against H. pylori infection, possibly due to the fact that Hp10 also induced substantial specific sIgA response at mucosal sites. Interestingly, when two lipopeptide vaccines were administrated in combination, Hp4 elevated the protective response against H. pylori infection of Hp10, which was characterized by better protective effect and enhanced specific T cell and mucosal antibody responses. Our results suggest that synthetic lipopeptide vaccines based on the epitopes derived from the protective antigens are promising candidates for protection against H. pylori infection.
2023-01-01 | GSE218459 | GEO
Project description:Biosynthesis of antimicrobial lipopeptide
| PRJNA635166 | ENA
Project description:Genomics of lipopeptide-producing Pseudmonas
Project description:We revealed that mycosubtilin, a lipopeptide from Bacillus subtilis, protects wheat against the hemibiotrophic fungal pathogen Zymoseptoria tritici. Foliar application of the biomolecule primes, during the early stages of infection, the expression of genes associated with sixteen functional groups, including responses to pathogens, abiotic and oxidative stresses, secondary metabolism, cell-wall structure and function, and primary metabolic pathways (carbohydrate, amino acid, protein, lipid, and energy metabolisms).
2022-11-04 | GSE169298 | GEO
Project description:Selection for glycopeptide, lipopeptide, and lipoglycopeptide-resistant MRSA
Project description:A putative lipopeptide biosynthetic gene cluster is conserved in many species of Actinobacteria, including Mycobacterium tuberculosis and Mycobacterium marinum, but the specific function of the encoding proteins has been elusive. Using both in vivo heterologous reconstitution and in vitro biochemical analyses, we have revealed that the five encoding biosynthetic enzymes are capable of synthesizing a new family of isonitrile lipopeptides (INLPs) through a thio-template mechanism. The biosynthesis features the generation of isonitrile from a single precursor Gly promoted by a thioesterase and a non-heme iron(II)-dependent oxidase homologue, and the acylation of both amino groups of Lys by the same isonitrile acyl chain facilitated by a single condensation domain of a non-ribosomal peptide synthetase (NRPS). In addition, the deletion of INLP biosynthetic genes in M. marinum has decreased the intracellular metal concentration, suggesting the role of this biosynthetic gene cluster in metal transport.
Project description:The soft rot pathogen Janthinobacterium agaricidamnosum causes devastating damage to button mushrooms (Agaricus bisporus), one of the most cultivated and commercially relevant mushrooms. We previously discovered that this pathogen releases the membrane-disrupting lipopeptide jagaricin. This bacterial toxin, however, could not solely explain the rapid decay of mushroom fruiting bodies, indicating that J. agaricidamnosum implements a more sophisticated infection strategy. In this study, we show that secretion systems play a crucial role in soft rot disease. By mining the genome of J. agaricidamnosum, we identified gene clusters encoding a type I (T1SS), a type II (T2SS), a type III (T3SS), and two type VI secretion systems (T6SS). Through a combination of knockout studies and bioassays, we found that the T2SS and T3SS of J. agaricidamnosum are required for soft rot disease. Furthermore, comparative secretome analysis and activity-guided fractionation identified a number of secreted lytic enzymes responsible for mushroom damage. Our findings regarding the contribution of secretion systems to the disease process expand the current knowledge of bacterial soft rot pathogens and represent a significant stride towards identifying targets for their disarmament with secretion system inhibitors.