Exploring the Impact of Amidation Status in Meso-Diaminopimelic-Acid-Containing Disaccharide Peptidoglycan Fragments on Host Innate Immune Activation

ACS Chemical Biology, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 3, 2025

Bacterial peptidoglycan, the essential cell surface polymer that protects bacterial integrity, also serves as molecular pattern recognized by host's innate immune system. Although minimal motifs of peptidoglycan fragments (PGNs) activate mammalian NOD1 and NOD2 sensors are well-known often represented small canonical ligands, immunostimulatory effects natural PGNs, which structurally more complex potentially can simultaneously both signaling pathways in hosts, have not been comprehensively investigated. In particular, many bacteria incorporate additional structural modifications peptidoglycans to evade host surveillance, resulting diverse variations among PGNs may influence their biological hosts. The focus this study is on amidation status γ-d-glutamic acid meso-diaminopimelic (mDAP) at second third positions stem peptides represent key features vary across different species. With four synthetic mDAP-containing disaccharide states, we systematically investigated structure–activity relationship stimulating responses vitro. Our findings revealed has distinct induction, along with differential activities macrophage cells. Additionally, found that, like ligand, confer tolerance LPS, states do affect outcome. Overall, our work highlights potential immunological implications these differentially amidated mDAP-type host–microbe crosstalk.

Language: Английский

Evaluation and Comparison of Candida albicans vs Mammalian 6-O-Phospho-Kinases: Substrate Specificity and Applications

Biochemistry, Journal Year: 2024, Volume and Issue: 64(1), P. 26 - 31

Published: Dec. 11, 2024

Sensing of peptidoglycan fragments is essential for inducing downstream signaling in both mammalian and fungal systems. The hexokinases NagK Hxk1 are crucial enzymes the phosphorylation molecules order to activate specific cellular responses; however, biochemical characterization their enzymatic specificity efficiency has yet be investigated depth. Here a mass spectrometry screen was implemented assess substrate specificity, an ATP coupled assay provided quantitative kinetic profiles these two homologous, eukaryotic enzymes. data show, that while have vastly different profiles. accepts variety peptidoglycan-based substrates albeit with reduced but still valuable as tool large scale chemoenzymatic settings. Conversely, smaller scope can turnover alternative at similar levels its natural substrate. These results allow deeper understanding into biosynthetic machinery responsible processes including UDP-GlcNAc regulation immune recognition events cell.

Language: Английский