Glycogen synthase kinase 3 inhibition controls Mycobacterium tuberculosis Infection

Compounds targeting host control of infectious diseases provide an attractive alternative to antimicrobials. A phenotypic screen of a kinase library identified compounds targeting glycogen synthase kinase 3 as potent inhibitors of Mycobacterium tuberculosis (Mtb) intracellular growth in the human THP-1 cell line and primary human monocytes-derived macrophages (hMDM). CRISPR knockouts and siRNA silencing showed that GSK3 isoforms are needed for the growth of Mtb and that a selected compound, P-4423632 targets GSK3β. GSK3 inhibition was associated with macrophage apoptosis governed by the Mtb secreted protein tyrosine phosphatase A (PtpA). Phospho-proteome analysis of macrophages response to infection revealed a wide array of host signaling and apoptosis pathways controlled by GSK3 and targeted by P-4423632. P-4423632 was additionally found to be active against other intracellular pathogens. Our findings strengthen the notion that targeting host signaling to promote the infected cell's in..., Lysates were prepared from parental or GSK3β knockout THP-1 cells (0.5 x 106 cells/well) that were differentiated overnight and then infected with WT Mtb or ΔptpA Mtb and treated with or without 10 µM P-4423632. Lysates were subjected to Kinexus Kinex™ KAM-2000 antibody microarray analyses as described (Yue, L., et al Clinical Proteomics & Bioinformatics. 2017;2(1):1-10). The KAM-2000 microarrays utilized 2059 commercial, pan-specific antibodies for 939 non-redundant human proteins targets that included protein kinases, phosphatases, transcription factors, stress proteins and many other signaling proteins. The KAM-2000 microarray featured 1165 pan-specific and 894 phosphosite-specific commercial antibodies, produced principally by Kinexus Bioinformatics (Vancouver, BC, Canada) as well as from other suppliers following their in-house validation, with each antibody printed in quadruplicate on each Nexterion P slide (Schott AG, Jena, Germany).
Two 16-bit images from each KAM-2000 micro..., Microsoft Excel
CAT-PETR (av-gay-ubc.shinyapps.io/CAT-PETR/): Flanagan K, Pelech S, Av-Gay Y, Dao Duc K. CAT PETR: A graphical user interface for differential analysis of phosphorylation data. Statistical Applications in Genetics and Molecular Biology. 2023 Aug 21;22(1). doi: 10.1515/sagmb-2023-0017., # Title: Glycogen Synthase Kinase 3 inhibition controls *Mycobacterium tuberculosis* Infection

[Access this dataset on Dryad](https://datadryad.org/stash/dataset/doi:10.5061/dryad.0rxwdbs5h)

Data showing modulation of macrophage phosphorylation upon infection and treatment with P-4423632 using antibody microarray analysis.

## Description of the data and file structure

The phosphorylation status of THP-1 cells were analysed from seven experimental conditions:
UP: Parental THP-1 cells, Uninfected, Untreated
IP: Parental THP-1 cells, Mtb-infected, Untreated
UPD1: Parental THP-1 cells, Uninfected, P-4423632-treated
IPD1: Parental THP-1 cells, Mtb-infected, P-4423632-treated
UO: GSK3B KO THP-1 cells, Uninfected, Untreated
IO: GSK3B KO THP-1 cells, Mtb-infected, Untreated
IPK01: Parental THP-1 cells, ptpA KO Mtb-infected, Untreated

#### Excel Data

Excel files include descriptions in the Read Me First tab
Excel File S1 compares UO and UPD1 to the UP control
Excel File S2 compares IO, IPD...