title: Mycobacterium tuberculosis strains exhibit differential and strain-specific molecular signatures in pulmonary epithelial cells.
abstract: Although pulmonary epithelial cells are integral to innate and adaptive immune responses during Mycobacterium tuberculosis infection, global transcriptomic changes in these cells remain largely unknown. Changes in gene expression induced in pulmonary epithelial cells infected with M. tuberculosis F15/LAM4/KZN, F11, F28, Beijing and Unique genotypes were investigated by RNA sequencing (RNA-Seq). The Illumina HiSeq 2000 platform generated 50 bp reads that were mapped to the human genome (Hg19) using Tophat (2.0.10). Differential gene expression induced by the different strains in infected relative to the uninfected cells was quantified and compared using Cufflinks (2.1.0) and MeV (4.0.9), respectively. Gene expression varied among the strains with the total number of genes as follows: F15/LAM4/KZN (1187), Beijing (1252), F11 (1639), F28 (870), Unique (886) and H37Rv (1179). A subset of 292 genes was commonly induced by all strains, where 52 genes were down-regulated while 240 genes were up-regulated. Differentially expressed genes were compared among the strains and the number of induced strain-specific gene signatures were as follows: F15/LAM4/KZN (138), Beijing (52), F11 (255), F28 (55), Unique (186) and H37Rv (125). Strain-specific molecular gene signatures associated with functional pathways were observed only for the Unique and H37Rv strains while certain biological functions may be associated with other strain signatures. This study demonstrated that strains of M. tuberculosis induce differential gene expression and strain-specific molecular signatures in pulmonary epithelial cells. Specific signatures induced by clinical strains of M. tuberculosis can be further explored for novel host-associated biomarkers and adjunctive immunotherapies.
authors: School of Life Sciences, College of Agriculture, Engineering and Science, University of KwaZulu-Natal, South Africa. Electronic address: mvubun@ukzn.ac.za.
authors: Nontobeko Eunice
authors: NE
authors: Mvubu
authors: School of Life Sciences, College of Agriculture, Engineering and Science, University of KwaZulu-Natal, South Africa. Electronic address: pillayb1@ukzn.ac.za.
authors: Balakrishna
authors: B
authors: Pillay
authors: South African National Bioinformatics Institute/MRC Unit for Bioinformatics Capacity Development, University of the Western Cape, South Africa. Electronic address: junaid@sanbi.ac.za.
authors: Junaid
authors: J
authors: Gamieldien
authors: Department of Medicine, Division of Infectious Diseases, Johns Hopkins School of Medicine, Baltimore, United States. Electronic address: wbishai1@jhmi.edu.
authors: William
authors: W
authors: Bishai
authors: Medical Microbiology and Infection Control, School of Laboratory Medicine and Medical Sciences, College of Health Sciences, University of KwaZulu-Natal, South Africa. Electronic address: pillayc@ukzn.ac.za.
authors: Manormoney
authors: M
authors: Pillay
mesh_terms: D056704:Adaptive Immunity; D002460:Cell Line; D004847:Epithelial Cells / Q000276:immunology / Q000382:microbiology*; D005786:Gene Expression Regulation; D005838:Genotype; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008168:Lung / Q000473:pathology*; D009169:Mycobacterium tuberculosis / Q000235:genetics* / Q000276:immunology; D013045:Species Specificity; D059467:Transcriptome; D014376:Tuberculosis / Q000276:immunology* / Q000382:microbiology
keywords: Differential gene expression; Molecular signatures; Mycobacterium tuberculosis; Pulmonary epithelial cells; Transcriptomics