Browse
Submit Data
Databases
API
Help

Dataset Information

8 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Catestatin in innate immunity and Cateslytin-derived peptides against superbugs.

ABSTRACT: Chromogranin A (CgA) is the precursor of several antimicrobial peptides, such as Catestatin (Cts, bovine CgA344-364), initially described as a potent inhibitor of catecholamines. This peptide displays direct antimicrobial activities and contributes to immune system regulation. The aim of the present study is to investigate a designed peptide based on Cts to fight infections against superbugs and more particularly Staphylococcus aureus. In addition to Cateslytin (Ctl, bovine CgA344-358), the active domain of Catestatin, several peptides including dimers, D-isomer and the new designed peptide DOPA-K-DOPA-K-DOPA-TLRGGE-RSMRLSFRARGYGFR (Dopa₅T-Ctl) were prepared and tested. Cateslytin is resistant to bacterial degradation and does not induce bacterial resistance. The interaction of Catestatin with immune dermal cells (dendritic cells DC1a, dermal macrophages CD14 and macrophages) was analyzed by using confocal microscopy and cytokine release assay. The dimers and D-isomer of Ctl were tested against a large variety of bacteria showing the potent antibacterial activity of the D-isomer. The peptide Dopa₅T-Ctl is able to induce the self-killing of S. aureus after release of Ctl by the endoprotease Glu-C produced by this pathogen. It permits localized on-demand delivery of the antimicrobial drug directly at the infectious site.

SUBMITTER: Scavello F

PROVIDER: S-EPMC8329280 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Hitchhiking with Nature: Snake Venom Peptides to Fight Cancer and Superbugs.

Project description:For decades, natural products in general and snake venoms (SV) in particular have been a rich source of bioactive compounds for drug discovery, and they remain a promising substrate for therapeutic development. Currently, a handful of SV-based drugs for diagnosis and treatment of various cardiovascular disorders and blood abnormalities are on the market. Likewise, far more SV compounds and their mimetics are under investigation today for diverse therapeutic applications, including antibiotic-resistant bacteria and cancer. In this review, we analyze the state of the art regarding SV-derived compounds with therapeutic potential, focusing on the development of antimicrobial and anticancer drugs. Specifically, information about SV peptides experimentally validated or predicted to act as antimicrobial and anticancer peptides (AMPs and ACPs, respectively) has been collected and analyzed. Their principal activities both in vitro and in vivo, structures, mechanisms of action, and attempts at sequence optimization are discussed in order to highlight their potential as drug leads.

| S-EPMC7232197 | biostudies-literature

Lymphocyte-derived ACh regulates local innate but not adaptive immunity.

Project description:Appropriate control of immune responses is a critical determinant of health. Here, we show that choline acetyltransferase (ChAT) is expressed and ACh is produced by B cells and other immune cells that have an impact on innate immunity. ChAT expression occurs in mucosal-associated lymph tissue, subsequent to microbial colonization, and is reduced by antibiotic treatment. MyD88-dependent Toll-like receptor up-regulates ChAT in a transient manner. Unlike the previously described CD4(+) T-cell population that is stimulated by norepinephrine to release ACh, ChAT(+) B cells release ACh after stimulation with sulfated cholecystokinin but not norepinephrine. ACh-producing B-cells reduce peritoneal neutrophil recruitment during sterile endotoxemia independent of the vagus nerve, without affecting innate immune cell activation. Endothelial cells treated with ACh in vitro reduced endothelial cell adhesion molecule expression in a muscarinic receptor-dependent manner. Despite this ability, ChAT(+) B cells were unable to suppress effector T-cell function in vivo. Therefore, ACh produced by lymphocytes has specific functions, with ChAT(+) B cells controlling the local recruitment of neutrophils.

| S-EPMC3557089 | biostudies-other

Database-Guided Discovery of Potent Peptides to Combat HIV-1 or Superbugs.

Project description:Antimicrobial peptides (AMPs), small host defense proteins, are indispensable for the protection of multicellular organisms such as plants and animals from infection. The number of AMPs discovered per year increased steadily since the 1980s. Over 2,000 natural AMPs from bacteria, protozoa, fungi, plants, and animals have been registered into the antimicrobial peptide database (APD). The majority of these AMPs (>86%) possess 11-50 amino acids with a net charge from 0 to +7 and hydrophobic percentages between 31-70%. This article summarizes peptide discovery on the basis of the APD. The major methods are the linguistic model, database screening, de novo design, and template-based design. Using these methods, we identified various potent peptides against human immunodeficiency virus type 1 (HIV-1) or methicillin-resistant Staphylococcus aureus (MRSA). While the stepwise designed anti-HIV peptide is disulfide-linked and rich in arginines, the ab initio designed anti-MRSA peptide is linear and rich in leucines. Thus, there are different requirements for antiviral and antibacterial peptides, which could kill pathogens via different molecular targets. The biased amino acid composition in the database-designed peptides, or natural peptides such as θ-defensins, requires the use of the improved two-dimensional NMR method for structural determination to avoid the publication of misleading structure and dynamics. In the case of human cathelicidin LL-37, structural determination requires 3D NMR techniques. The high-quality structure of LL-37 provides a solid basis for understanding its interactions with membranes of bacteria and other pathogens. In conclusion, the APD database is a comprehensive platform for storing, classifying, searching, predicting, and designing potent peptides against pathogenic bacteria, viruses, fungi, parasites, and cancer cells.

| S-EPMC3816732 | biostudies-literature

Defense Peptides From the ?-Hairpinin Family Are Components of Plant Innate Immunity.

Project description:Plant immunity represents a sophisticated system, including both basal and inducible mechanisms, to prevent pathogen infection. Antimicrobial peptides (AMPs) are among the innate immunity components playing a key role in effective and rapid response against various pathogens. This review is devoted to a small family of defense peptides called ?-hairpinins. The general characters of the family, as well as the individual features of each member, including biological activities, structures of precursor proteins, and spatial structures, are described. Possible applications of ?-hairpinin peptides in drug design are discussed.

| S-EPMC7191063 | biostudies-literature

Sensor molecules in intestinal innate immunity against bacterial infections.

Project description:Toll-like receptors (TLRs) and nucleotide-binding oligomerization domain (NOD)-containing proteins are innate immune sensors for microbial signature molecules. This review highlights new insights into the functions of these sensors in intestinal physiology.TLRs are membrane bound and survey the extracellular space for microbe-derived molecules, while NOD-containing proteins are cytoplasmic and detect microbial molecules in the cytoplasm. Most microbial sensors recognize components of the bacterial cell wall and its appendages. For example, TLR4 detects lipopolysaccharide in the Gram-negative bacterial cell wall. TLR5 recognizes flagellin, a component of bacterial flagella required for motility. NOD1 recognizes diaminopimelic acid-containing dipeptide or tripeptide motifs in the Gram-positive bacterial cell wall, while NOD2 detects muramyl dipeptide, a ubiquitous cell wall peptidoglycan motif. These sensors are important for host defense against gastrointestinal pathogens. Thus, TLR4 is required for Salmonella eradication, NOD1 contributes to controlling Helicobacter pylori infection, and NOD2 is involved in mucosal defense against Listeria monocytogenes. These sensors also regulate mucosal inflammation independent of pathogen infections.Toll-like receptors and nucleotide-binding oligomerization domain-containing proteins not only play critical roles in host defense against known gastrointestinal bacterial pathogens, but also contribute to mucosal homeostasis in the apparent absence of such pathogens.

| S-EPMC2695762 | biostudies-literature

Kidney dendritic cells induce innate immunity against bacterial pyelonephritis.

Project description:Dendritic cells (DCs) are the most abundant immune cells in the kidney and form an intricate network in the tubulointerstitium, suggesting that they may play an important role in interstitial infections such as pyelonephritis. Here, we optimized a murine pyelonephritis model by instilling uropathogenic Escherichia coli two times at a 3-hour interval, which produced an infection rate of 84%. By 3 hours after the second instillation, resident kidney DCs began secreting the chemokine CXCL2, which recruits neutrophilic granulocytes. During the time studied, DCs remained responsible for most of the CXCL2 production. Neutrophils began infiltrating the kidney 3 hours after the second instillation and phagocytozed bacteria. Macrophages followed 3 hours later and contributed much less to both CXCL2 production and bacterial phagocytosis. To investigate whether DCs recruit neutrophils into the kidney for antibacterial defense, we used CD11c.DTR mice allowing conditional depletion of CD11c(+) dendritic cells. The absence of CD11c(+) DCs markedly delayed neutrophil recruitment and bacterial clearance. In conclusion, these findings suggest that the tubulointerstitial dendritic cell network serves an innate immune sentinel function against bacterial pyelonephritis.

| S-EPMC3148698 | biostudies-literature

Pangolin scales as adaptations for innate immunity against pathogens

Project description:In this study, we used stringent criteria to identify prominent proteins and metabolites for downstream analyses. For scale proteins, we reported a prominent protein if a protein presented in at least five out of six experimental sets with sequence identify of at least 96%. For skin surface proteins, we defined a prominent protein as a protein that presented in at least two out of three experimental sets with sequence identify of at least 96%.

2024-08-23 | PXD052288 | Pride

Human T-bet Governs Innate and Innate-like Adaptive IFN-γ Immunity against Mycobacteria.

Project description:Inborn errors of human interferon gamma (IFN-γ) immunity underlie mycobacterial disease. We report a patient with mycobacterial disease due to inherited deficiency of the transcription factor T-bet. The patient has extremely low counts of circulating Mycobacterium-reactive natural killer (NK), invariant NKT (iNKT), mucosal-associated invariant T (MAIT), and Vδ2+ γδ T lymphocytes, and of Mycobacterium-non reactive classic TH1 lymphocytes, with the residual populations of these cells also producing abnormally small amounts of IFN-γ. Other lymphocyte subsets develop normally but produce low levels of IFN-γ, with the exception of CD8+ αβ T and non-classic CD4+ αβ TH1∗ lymphocytes, which produce IFN-γ normally in response to mycobacterial antigens. Human T-bet deficiency thus underlies mycobacterial disease by preventing the development of innate (NK) and innate-like adaptive lymphocytes (iNKT, MAIT, and Vδ2+ γδ T cells) and IFN-γ production by them, with mycobacterium-specific, IFN-γ-producing, purely adaptive CD8+ αβ T, and CD4+ αβ TH1∗ cells unable to compensate for this deficit.

| S-EPMC7770098 | biostudies-literature

Murine and bovine ?? T cells enhance innate immunity against Brucella abortus infections.

Project description:?? T cells have been postulated to act as a first line of defense against infectious agents, particularly intracellular pathogens, representing an important link between the innate and adaptive immune responses. Human ?? T cells expand in the blood of brucellosis patients and are active against Brucella in vitro. However, the role of ?? T cells in vivo during experimental brucellosis has not been studied. Here we report TCR?(-/-) mice are more susceptible to B. abortus infection than C57BL/6 mice at one week post-infection as measured by splenic colonization and splenomegaly. An increase in TCR?? cells was observed in the spleens of B. abortus-infected C57BL/6 mice, which peaked at two weeks post-infection and occurred concomitantly with diminished brucellae. ?? T cells were the major source of IL-17 following infection and also produced IFN-?. Depletion of ?? T cells from C57BL/6, IL-17R?(-/-), and GMCSF(-/-) mice enhanced susceptibility to B. abortus infection although this susceptibility was unaltered in the mutant mice; however, when ?? T cells were depleted from IFN-?(-/-) mice, enhanced susceptibility was observed. Neutralization of ?? T cells in the absence of TNF-? did not further impair immunity. In the absence of TNF-? or ?? T cells, B. abortus-infected mice showed enhanced IFN-?, suggesting that they augmented production to compensate for the loss of ?? T cells and/or TNF-?. While the protective role of ?? T cells was TNF-?-dependent, ?? T cells were not the major source of TNF-? and activation of ?? T cells following B. abortus infection was TNF-?-independent. Additionally, bovine TCR?? cells were found to respond rapidly to B. abortus infection upon co-culture with autologous macrophages and could impair the intramacrophage replication of B. abortus via IFN-?. Collectively, these results demonstrate ?? T cells are important for early protection to B. abortus infections.

| S-EPMC3134454 | biostudies-other

RNA interference directs innate immunity against viruses in adult Drosophila.

Project description:Innate immunity against bacterial and fungal pathogens is mediated by Toll and immune deficiency (Imd) pathways, but little is known about the antiviral response in Drosophila. Here, we demonstrate that an RNA interference pathway protects adult flies from infection by two evolutionarily diverse viruses. Our work also describes a molecular framework for the viral immunity, in which viral double-stranded RNA produced during infection acts as the pathogen trigger whereas Drosophila Dicer-2 and Argonaute-2 act as host sensor and effector, respectively. These findings establish a Drosophila model for studying the innate immunity against viruses in animals.

| S-EPMC1509097 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data