Montano, E. | Search bioRxiv

bioRxiv2024

Alterations in genes associated with cytosolic RNA sensing in whole blood are associated with coronary microvascular disease in SLE

ObjectiveTo investigate whether gene signatures discriminate systemic lupus erythematosus (SLE) patients with coronary microvascular dysfunction (CMD) from those without and whether any signaling pathway is linked to the underlying pathobiology of SLE CMD. MethodsThis study collected whole blood RNA samples from female subjects aged 37 to 57, comprising 11 SLE patients (4 SLE-CMD, 7 SLE-non-CMD) and 10 HC. Total RNA was then used for library preparation and sequencing. Differential gene expression analysis was performed to identify gene signatures associated with CMD in SLE patients using DEseq2 v1.42.0. Gene Set Enrichment Analysis were performed by ClusterProfiler v4.10.0 and pathfindR v2.3.1. ResultsRNA-seq analysis revealed 143 differentially expressed (DE) genes between the SLE and HC groups. GO analysis indicated associations with virus defense and interferon signaling in SLE. 14 DE genes were identified from comparison between SLE-CMD and SLE-non-CMD with adjusted parameters (padj < 0.1). Notably, SLE-CMD exhibited elevated levels of genes associated with RNA sensing, while downregulated genes in SLE-non-CMD were associated with blood coagulation and cell-cell junction. Further investigation highlighted differences in IFN signaling and ADP-ribosylation pathways between SLE-CMD and SLE-non-CMD, suggesting distinct molecular mechanisms underlying vascular changes in CMD and reduced left ventricular function in non-CMD. ConclusionOur study identified a unique gene signature in SLE-CMD compared to the HC group, highlighting the significant involvement of type 1 interferon, RIG-I family proteins, and chronic inflammation in the progression of SLE-CMD. The intricate relationship between SLE-CMD and these factors underscores their probable role in initiating and advancing SLE-CMD.

bioinformatics↗

bioRxiv2022

Strengthening of enterococcal biofilms by Esp

Multidrug-resistant (MDR) Enterococcus faecalis are major causes of hospital-acquired infections. Numerous clinical strains harbor a large pathogenicity island that encodes enterococcal surface protein (Esp), which is suggested to promote biofilm production and virulence, but this remains controversial. To resolve this issue, we characterized the Esp N-terminal region, the portion implicated in biofilm production. Small angle X-ray scattering indicated that the N-terminal region had a globular head, which consisted of two DEv-Ig domains as visualized by X-ray crystallography, followed by an extended tail. The N-terminal region was not required for biofilm production but instead significantly strengthened biofilms against mechanical or degradative disruption, greatly increasing retention of Enterococcus within biofilms. Biofilm strengthening required low pH, which resulted in Esp unfolding, aggregating, and forming amyloid-like structures. The pH threshold for biofilm strengthening depended on protein stability. A truncated fragment of the first DEv-Ig domain, plausibly generated by a host protease, was the least stable and sufficient to strengthen biofilms at pH [≤] 5.0, while the entire N-terminal region and intact Esp on the enterococcal surface was more stable and required a pH [≤] 4.3. These results suggested a virulence role of Esp in strengthening enterococcal biofilms in acidic abiotic or host environments.

microbiology↗