PMID- 30222739
OWN - NLM
STAT- MEDLINE
DCOM- 20190114
LR  - 20240313
IS  - 1935-2735 (Electronic)
IS  - 1935-2727 (Print)
IS  - 1935-2727 (Linking)
VI  - 12
IP  - 9
DP  - 2018 Sep
TI  - Phospho-proteomic analysis of primary human colon epithelial cells during the 
      early Trypanosoma cruzi infection phase.
PG  - e0006792
LID - 10.1371/journal.pntd.0006792 [doi]
LID - e0006792
AB  - The protozoan parasite Trypanosoma cruzi, the causative agent of Chagas disease, 
      causes severe morbidity and mortality in afflicted individuals. About 30% of T. 
      cruzi-infected individuals present with cardiac, gastrointestinal tract, and/or 
      neurological disorders. Megacolon, one of the major pathologies of Chagas 
      disease, is accompanied by gastrointestinal motility disorders. The molecular 
      mechanism of T. cruzi-mediated megacolon in Chagas disease is currently unknown. 
      To decipher the molecular mechanism of T. cruzi-induced alteration in the colon 
      during the early infection phase, we exposed primary human colonic epithelial 
      cells (HCoEpiC) to invasive T. cruzi trypomastigotes at multiple time points to 
      determine changes in the phosphoprotein networks in the cells following infection 
      using proteome profiler Human phospho-kinase arrays. We found significant changes 
      in the phosphorylation pattern that can mediate cellular deregulations in colonic 
      epithelial cells after infection. We detected a significant increase in the 
      levels of phosphorylated heat shock protein (p-HSP) 27 and transcription factors 
      that regulate various cellular functions, including c-Jun and CREB. Our study 
      confirmed significant upregulation of phospho (p-) Akt S473, p-JNK, which may 
      directly or indirectly modulate CREB and c-Jun phosphorylation, respectively. We 
      also observed increased levels of phosphorylated CREB and c-Jun in the nucleus. 
      Furthermore, we found that p-c-Jun and p-CREB co-localized in the nucleus at 180 
      minutes post infection, with a maximum Pearson correlation coefficient of 
      0.76+/-0.02. Increased p-c-Jun and p-CREB have been linked to inflammatory and 
      profibrotic responses. T. cruzi infection of HCoEpiC induces an increased 
      expression of thrombospondin-1 (TSP-1), which is fibrogenic at elevated levels. 
      We also found that T. cruzi infection modulates the expression of NF-kB and 
      JAK2-STAT1 signaling molecules which can increase pro-inflammatory flux. 
      Bioinformatics analysis of the phosphoprotein networks derived using the 
      phospho-protein data serves as a blueprint for T. cruzi-mediated cellular 
      transformation of primary human colonic cells during the early phase of T. cruzi 
      infection.
FAU - Suman, Shankar
AU  - Suman S
AD  - Department of Microbiology and Immunology, Meharry Medical College, Nashville, 
      Tennessee, United States of America.
FAU - Rachakonda, Girish
AU  - Rachakonda G
AD  - Department of Microbiology and Immunology, Meharry Medical College, Nashville, 
      Tennessee, United States of America.
FAU - Mandape, Sammed N
AU  - Mandape SN
AD  - Department of Microbiology and Immunology, Meharry Medical College, Nashville, 
      Tennessee, United States of America.
FAU - Sakhare, Shruti S
AU  - Sakhare SS
AD  - Department of Microbiology and Immunology, Meharry Medical College, Nashville, 
      Tennessee, United States of America.
FAU - Villalta, Fernando
AU  - Villalta F
AD  - Department of Microbiology and Immunology, Meharry Medical College, Nashville, 
      Tennessee, United States of America.
FAU - Pratap, Siddharth
AU  - Pratap S
AUID- ORCID: 0000-0003-2200-0848
AD  - School of Graduate Studies and Research, Meharry Medical College, Nashville, 
      Tennessee, United States of America.
FAU - Lima, Maria F
AU  - Lima MF
AD  - School of Graduate Studies and Research, Meharry Medical College, Nashville, 
      Tennessee, United States of America.
FAU - Nde, Pius N
AU  - Nde PN
AUID- ORCID: 0000-0001-7101-7721
AD  - Department of Microbiology and Immunology, Meharry Medical College, Nashville, 
      Tennessee, United States of America.
LA  - eng
GR  - S21 MD000104/MD/NIMHD NIH HHS/United States
GR  - U54 MD007593/MD/NIMHD NIH HHS/United States
GR  - SC1 AI127352/AI/NIAID NIH HHS/United States
GR  - R25 GM059994/GM/NIGMS NIH HHS/United States
GR  - U54 MD010722/MD/NIMHD NIH HHS/United States
GR  - U54 MD007586/MD/NIMHD NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20180917
PL  - United States
TA  - PLoS Negl Trop Dis
JT  - PLoS neglected tropical diseases
JID - 101291488
RN  - 0 (Phosphoproteins)
RN  - 0 (Proteome)
SB  - IM
MH  - Cells, Cultured
MH  - Chagas Disease/*pathology
MH  - Colon/*pathology
MH  - Epithelial Cells/*pathology
MH  - Humans
MH  - Models, Biological
MH  - Phosphoproteins/*analysis
MH  - Proteome/*analysis
MH  - Proteomics
MH  - Trypanosoma cruzi/*growth & development
PMC - PMC6160231
COIS- The authors have declared that no competing interests exist.
EDAT- 2018/09/18 06:00
MHDA- 2019/01/15 06:00
PMCR- 2018/09/17
CRDT- 2018/09/18 06:00
PHST- 2018/04/19 00:00 [received]
PHST- 2018/08/27 00:00 [accepted]
PHST- 2018/09/27 00:00 [revised]
PHST- 2018/09/18 06:00 [pubmed]
PHST- 2019/01/15 06:00 [medline]
PHST- 2018/09/18 06:00 [entrez]
PHST- 2018/09/17 00:00 [pmc-release]
AID - PNTD-D-18-00642 [pii]
AID - 10.1371/journal.pntd.0006792 [doi]
PST - epublish
SO  - PLoS Negl Trop Dis. 2018 Sep 17;12(9):e0006792. doi: 
      10.1371/journal.pntd.0006792. eCollection 2018 Sep.