Dataset Information

Target identification of usnic acid in bacterial and human cells

ABSTRACT: Usnic acid is a natural product with versatile biological activities against various organisms. We here utilize a chemical proteomic strategy to gain insights into its target scope in bacterial and human cells. First, we excluded DNA binding as a major reason for its antibacterial activity and second commenced with target profiling which unravelled several metal cofactor-dependent enzymes in both species. This is in line with the metal complexation activities of usnic acid and suggests a polypharmacological mode of action. Interestingly, our synthetic studies revealed a selectivity switch at usnic acid which maintains antibacterial activity but lacks strong cytotoxic effects.

INSTRUMENT(S): Q Exactive HF

ORGANISM(S): Enterococcus Faecalis (streptococcus Faecalis) Homo Sapiens (human)

TISSUE(S): Cell Culture

SUBMITTER: Dietrich Mostert

LAB HEAD: Stephan A. Sieber

PROVIDER: PXD049013 | Pride | 2024-08-10

REPOSITORIES: Pride

ACCESS DATA

Dataset's files

Source:

			Action	DRS
	20200924_SR_20200907_HeLa_01_DMSO_DMSO.raw	Raw
	20200924_SR_20200907_HeLa_03_DMSO_DMSO.raw	Raw
	20200924_SR_20200907_HeLa_04_DMSO_DMSO.raw	Raw
	20200924_SR_20200907_HeLa_05_DMSO_SR136a_20uM.raw	Raw
	20200924_SR_20200907_HeLa_06_DMSO_SR136a_20uM.raw	Raw

Items per page:

1 - 5 of 51

Publications

Target identification of usnic acid in bacterial and human cells.

Ruddell Stuart A SA Mostert Dietrich D Sieber Stephan A SA

RSC chemical biology 20240507 7

Usnic acid is a natural product with versatile biological activities against various organisms. Here, we utilise a chemical proteomic strategy to gain insights into its target scope in bacterial and human cells. First, we excluded DNA binding as a major reason for its antibacterial activity, and second, we commenced with target profiling, which unravelled several metal cofactor-dependent enzymes in both species indicating a polypharmacological mode of action. Interestingly, our synthetic studies ...[more]

PMID: 38966671

Similar Datasets

Project description:Glycans are key to host-pathogen interactions, whereby recognition by the host and immunomodulation by the pathogen can be mediated by carbohydrate binding proteins, such as lectins of the innate immune system, and their glycoconjugate ligands. Previous studies have shown that excretory-secretory products of the porcine nematode parasite Trichuris suis exert immunomodulatory effects in a glycan-dependent manner. To better understand the mechanisms of these interactions, we prepared N-glycans from T. suis and both analyzed their structures and used them to generate a natural glycan microarray. With this array we explored the interactions of glycans with C-type lectins, C-reactive protein and sera from T. suis infected pigs. Glycans containing LacdiNAc and phosphorylcholine-modified glycans were associated with the highest binding by most of these proteins. In-depth analysis revealed not only fucosylated LacdiNAc motifs with and without phosphorylcholine moieties, but phosphorylcholine-modified mannose and N-acetylhexosaminesubstituted fucose residues, in the context of maximally tetraantennary N-glycan scaffolds. Furthermore, O-glycans also contained fucosylated motifs. In summary, the glycans of T. suis are recognized by both the innate and adaptive immune systems, and also exhibit species-specific features distinguishing its glycome from those of other nematodes.Glycans are key to host-pathogen interactions, whereby recognition by the host and immunomodulation by the pathogen can be mediated by carbohydrate binding proteins, such as lectins of the innate immune system, and their glycoconjugate ligands. Previous studies have shown that excretory-secretory products of the porcine nematode parasite Trichuris suis exert immunomodulatory effects in a glycan-dependent manner. To better understand the mechanisms of these interactions, we prepared N-glycans from T. suis and both analyzed their structures and used them to generate a natural glycan microarray. With this array we explored the interactions of glycans with C-type lectins, C-reactive protein and sera from T. suis infected pigs. Glycans containing LacdiNAc and phosphorylcholine-modified glycans were associated with the highest binding by most of these proteins. In-depth analysis revealed not only fucosylated LacdiNAc motifs with and without phosphorylcholine moieties, but phosphorylcholine-modified mannose and N-acetylhexosaminesubstituted fucose residues, in the context of maximally tetraantennary N-glycan scaffolds. Furthermore, O-glycans also contained fucosylated motifs. In summary, the glycans of T. suis are recognized by both the innate and adaptive immune systems, and also exhibit species-specific features distinguishing its glycome from those of other nematodes.