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Levi, Z.

Publications and source records attributed to Levi, Z..

2 recordsLinked to original sources

A phage communication peptide alters Bacillus subtilis colony development and promotes sporulation

Temperate Bacillus phages use arbitrium peptides to coordinate lysis-lysogeny decisions, but whether the mature communication peptide can be sensed directly by Bacillus subtilis and affect its physiology and behavior is unknown. Here we show that the {varphi}3T arbitrium peptide SAIRGA elicits a sequence- and stereochemistry-dependent response in Bacillus subtilis that is strongly expressed in surface-grown colony biofilms but is not accompanied by comparable changes in planktonic growth or static-liquid pellicle morphology. The response persists in the absence of AimR, the canonical arbitrium receptor. Within colonies, SAIRGA alters spatial PtapA activity and increases heat-resistant spore formation without increasing total viable cell yield. Untargeted metabolomics reveals broad dose-dependent remodeling that tracks peptide activity, while program-level proteomics independently converges on late-sporulation and mature-spore-associated states. This study highlights how a phage-derived peptide may act as a signal, enabling the host to pivot toward a survival-focused developmental state.

microbiology↗

Discordant effects of ex-vivo JAK inhibition on inflammatory responses in colonic compared to ileal mucosa

Background & aimsJanus kinase (JAK) inhibitors modulating JAK-STAT (signal transducers and activators of transcription) signaling pathway, are used for the treatment of patients with inflammatory bowel diseases (IBD). We aimed to identify the molecular effects of JAK inhibition in the human intestinal mucosa, considering the IBD location and phenotype. MethodsColonic and ileal explants from patients with ulcerative colitis (UC), Crohns disease (CD), or non-IBD controls (NC) were treated ex-vivo with the JAK inhibitor, tofacitinib. Phosphorylated STAT (p-STAT) levels were assessed by Western blot and Immunofluorescence. Inflammatory genes expression was assessed with Nanostring nCounter system. Human intestinal organoids were used to assess JAK inhibitors effects on p-STATs and iNOS expression. ResultsExplants were collected from 68 patients (NC=28; UC=20; CD=20). JAK inhibition reduced p-STAT1/3/5 expression in all explants. While p-STAT inhibition rates varied among patients (10%-88%), higher inhibition rates were observed in colonic compared to ileal explants. Significant alterations in 120 of 255 inflammatory genes were observed in colonic explants, while only 30 were observed in ileal NC explants. In colonic explants from UC, significant alterations were observed in 5 genes, including STAT1 and NOS2. Various JAK inhibitors reduced IFN-{gamma}-induced increase in p-STAT1 and iNOS expression in organoids. ConclusionsA site-specific anti-inflammatory effect of JAK inhibition by tofacitinib was noticed, whereby the colon was more robustly affected than the ileum. Ex-vivo response to tofacitinib is individual. JAK inhibition may attenuate inflammation by decreasing iNOS expression. Ex-vivo mucosal platforms may be a valuable resource for studying drug impact and evaluating personalized treatment effects.

immunology↗