TY - JOUR
T1 - Canonical pathways, networks and transcriptional factor regulation by clinical strains of Mycobacterium tuberculosis in pulmonary alveolar epithelial cells
AU - Mvubu, Nontobeko E.
AU - Pillay, Balakrishna
AU - Gamieldien, Junaid
AU - Bishai, William
AU - Pillay, Manormoney
N1 - Funding Information:
We gratefully acknowledge Mrs N. Naidoo and Mr T. Mkize for editing and proof-reading the manuscript, the National Research Foundation (UID; 83846 ) and the KwaZulu-Natal Research Institute for Tuberculosis and HIV for financial support, and Miss D. Geiman for technical assistance at Johns Hopkins University (USA).
Publisher Copyright:
© 2015 Elsevier Ltd. All rights reserved.
PY - 2016/3
Y1 - 2016/3
N2 - Summary Limited knowledge exists on pathways, networks and transcriptional factors regulated within epithelial cells by diverse Mycobacterium tuberculosis genotypes. This study aimed to elucidate these mechanisms induced in A549 epithelial cells by dominant clinical strains in KwaZulu-Natal, South Africa. RNA for sequencing was extracted from epithelial cells at 48 h post-infection with 5 strains at a multiplicity of infection of approximately 10:1. Bioinformatics analysis performed with the RNA-Seq Tuxedo pipeline identified differentially expressed genes. Changes in pathways, networks and transcriptional factors were identified using Ingenuity Pathway Analysis (IPA). The interferon signalling and hepatic fibrosis/hepatic stellate cell activation pathways were among the top 5 canonical pathways in all strains. Hierarchical clustering for enrichment of cholesterol biosynthesis and immune associated pathways revealed similar patterns for Beijing and Unique; F15/LAM4/KZN and F11; and, F28 and H37Rv strains, respectively. However, the induction of top scoring networks varied among the strains. Among the transcriptional factors, only EHL, IRF7, PML, STAT1, STAT2 and VDR were induced by all clinical strains. Activation of the different pathways, networks and transcriptional factors revealed in the current study may be an underlying mechanism that results in the differential host response by clinical strains of M. tuberculosis.
AB - Summary Limited knowledge exists on pathways, networks and transcriptional factors regulated within epithelial cells by diverse Mycobacterium tuberculosis genotypes. This study aimed to elucidate these mechanisms induced in A549 epithelial cells by dominant clinical strains in KwaZulu-Natal, South Africa. RNA for sequencing was extracted from epithelial cells at 48 h post-infection with 5 strains at a multiplicity of infection of approximately 10:1. Bioinformatics analysis performed with the RNA-Seq Tuxedo pipeline identified differentially expressed genes. Changes in pathways, networks and transcriptional factors were identified using Ingenuity Pathway Analysis (IPA). The interferon signalling and hepatic fibrosis/hepatic stellate cell activation pathways were among the top 5 canonical pathways in all strains. Hierarchical clustering for enrichment of cholesterol biosynthesis and immune associated pathways revealed similar patterns for Beijing and Unique; F15/LAM4/KZN and F11; and, F28 and H37Rv strains, respectively. However, the induction of top scoring networks varied among the strains. Among the transcriptional factors, only EHL, IRF7, PML, STAT1, STAT2 and VDR were induced by all clinical strains. Activation of the different pathways, networks and transcriptional factors revealed in the current study may be an underlying mechanism that results in the differential host response by clinical strains of M. tuberculosis.
KW - Canonical pathways
KW - Epithelial cells
KW - Mycobacterium tuberculosis
KW - Networks
KW - RNA sequencing
KW - Transcriptional factors
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U2 - 10.1016/j.tube.2015.12.002
DO - 10.1016/j.tube.2015.12.002
M3 - Article
C2 - 26980499
AN - SCOPUS:84960394449
VL - 97
SP - 73
EP - 85
JO - Bulletin of the International Union Against Tuberculosis and Lung Disease
JF - Bulletin of the International Union Against Tuberculosis and Lung Disease
SN - 1472-9792
ER -