Biology subjects

Hendrickson, A.

Publications and source records attributed to Hendrickson, A..

3 recordsLinked to original sources

bioRxiv2025

Lactuchelins: New lipopeptide siderophores from Pseudomonas lactucae inhibit Xanthomonas campestris pv. campestris 8004

Seeds harbor diverse microbial communities, including beneficial microbes that play a vital role in protecting plants from seed-borne pathogens. Despite their critical importance, the molecular mechanisms driving intermicrobial competition within the seed microbiome remain poorly understood, limiting the potential to optimize seed inoculation strategies. In this study, we evaluated the inhibitory potential of 30 seed-borne bacterial strains against the phytopathogen Xanthomonas campestris pv. campestris 8004 (Xcc8004). We identified Pseudomonas lactucae CFBP13502 as a potent inhibitor of Xcc8004, mediated by exometabolites specifically induced in the presence of Lysobacterales (formerly Xanthomonadales). Transcriptomic analysis of CFBP13502 revealed upregulation of a gene cluster involved in the biosynthesis of a lipopeptide siderophore biosynthesis. Gene deletion confirmed that this cluster is essential for the growth inhibition of Xcc8004. Furthermore, iron supplementation abolished this inhibitory effect, providing strong evidence for the role of iron chelation. Through comparative metabolomics, we elucidated the structure of a novel family of lipopeptide siderophores, which we named lactuchelins, produced by CFBP13502. Our findings provide the first molecular evidence of competitive exclusion mechanisms at the seed microbiome interface, highlighting lactuchelins as a promising avenue for the development of seed-based biocontrol strategies against seed-borne phytopathogens.

microbiology↗

bioRxiv2024

The CECR2 bromodomain displays distinct binding modes to select for acetylated histone proteins versus non-histone ligands.

The cat eye syndrome chromosome region candidate 2 (CECR2) protein is an epigenetic regulator involved in chromatin remodeling and transcriptional control. The CECR2 bromodomain (CECR2-BRD) plays a pivotal role in directing the activity of CECR2 through its capacity to recognize and bind acetylated lysine residues on histone proteins. This study elucidates the binding specificity and structural mechanisms of CECR2-BRD interactions with both histone and non-histone ligands, employing techniques such as isothermal titration calorimetry (ITC), nuclear magnetic resonance (NMR) spectroscopy, and a high-throughput peptide assay. The CECR2-BRD selectively binds acetylated histone H3 and H4 ligands, exhibiting a preference for multi-acetylated over mono-acetylated targets. The highest affinity was observed for tetra-acetylated histone H4. Neighboring post-translational modifications, including methylation and phosphorylation, modulate acetyllysine recognition, with significant effects observed for histone H3 ligands. Additionally, this study explored the interaction of the CECR2-BRD with the acetylated RelA subunit of NF-{kappa}B, a pivotal transcription factor in inflammatory signaling. Dysregulated NF-{kappa}B signaling is implicated in numerous pathologies, including cancer progression, with acetylation of RelA at lysine 310 (K310ac) being critical for its transcriptional activity. Recent evidence linking the CECR2-BRD to RelA suggests it plays a role in inflammatory and metastatic pathways, underscoring the need to understand the molecular basis of this interaction. We found the CECR2-BRD binds to acetylated RelA with micromolar affinity, and uses a distinctive binding mode to recognize this non-histone ligand. These results provide new insight on the role of CECR2 in regulating NF-{kappa}B-mediated inflammatory pathways. Functional mutagenesis of critical residues, such as Asn514 and Asp464, highlight their roles in ligand specificity and binding dynamics. Notably, the CECR2-BRD remained monomeric in solution and exhibited differential conformational responses upon ligand binding, suggesting adaptive recognition mechanisms. Furthermore, the CECR2-BRD exclusively interacts with nucleosome substrates containing multi-acetylated histones, emphasizing its role in transcriptional activation within euchromatic regions. These findings position the CECR2-BRD as a key chromatin reader and a promising therapeutic target for modulating transcriptional and inflammatory processes, particularly through the development of selective bromodomain inhibitors. HIGHLIGHTSO_LIThe CECR2 bromodomain recognizes a range of combinatorial PTMs on the histone H3 and H4 N-terminal tails. C_LIO_LIThe CECR2 bromodomain binds to an acetylated RelA ligand with micromolar affinity. C_LIO_LINMR perturbation studies delineate the distinct binding modes driving CECR2-BRD recognition of histone versus non-histone ligands. C_LIO_LISite-directed mutagenesis reveals the specificity determinants of CECR2-BRD ligand binding. C_LIO_LIThe bromodomain of CECR2 exhibits a strong interaction with multi-acetylated nucleosomes. C_LI

biochemistry↗

bioRxiv2024

Influence of chondroitin sulfate glycan sulfation patterns on histochemical labeling of perineuronal nets- a comparative study of interregional distribution in human and mouse brain

Perineuronal nets (PNNs) are a condensed subtype of extracellular matrix that form a net-like coverings around certain neurons in the brain. PNNs are primarily composed of chondroitin sulfate (CS) proteoglycans from the lectican family that consist of CS-glycosaminoglycan (CS-GAG) side chains attached to a core protein. CS disaccharides can exist in various isoforms with different sulfation patterns. Literature suggests that CS disaccharide sulfation patterns can influence the function of PNNs as well as their labeling. This study was conducted to characterize such interregional CS disaccharide sulfation pattern differences in adult human (N = 81) and mouse (N = 19) brains. Liquid chromatography tandem mass spectrometry was used to quantify five different CS disaccharide sulfation patterns, which were then compared to immunolabeling of PNNs using Wisteria Floribunda Lectin (WFL) to identify CS-GAGs and anti-aggrecan to identify CS proteoglycans. In healthy brains, significant regional and species-specific differences in CS disaccharide sulfation and single versus double-labeling pattern were identified. A secondary analysis to investigate how early-life stress (ELS) impacts these PNN features discovered that although ELS increases WFL+ PNN density, the CS-GAG sulfation code and single versus double PNN-labeling distributions remained unaffected in both species. These results underscore PNN complexity in traditional research, emphasizing the need to consider their heterogeneity in future experiments.

neuroscience↗