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Quantitative phosphoproteome analyses of human macrophage-like THP-1 cells following infection with virulent Mycobacterium tuberculosis and avirulent M. bovis BCG, respectively.

ABSTRACT: In this project we conducted a comprehensive analysis of expression and global phosphorylation status of the host proteins following infection with virulent and avirulent mycobacteria. Our objective is to identify previously uncharacterized proteins of host macrophages that are specifically expressed and phosphorylated in response to Mtb and BCG, respectively and may play important role in regulating their intracellular survival

INSTRUMENT(S): LTQ Orbitrap

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Macrophage

DISEASE(S): Pulmonary Tuberculosis

SUBMITTER: Renu Goel

LAB HEAD: Dr. Nisheeth Agarwal

PROVIDER: PXD013171 | Pride | 2020-05-15

REPOSITORIES: Pride

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			Action	DRS
	tc_s293p_F10_z05556.raw	Raw
	tc_s293p_F11_z05557.raw	Raw
	tc_s293p_F12_z05558.raw	Raw
	tc_s293p_F1_z05547.raw	Raw
	tc_s293p_F2_z05548.raw	Raw

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Publications

Relative and Quantitative Phosphoproteome Analysis of Macrophages in Response to Infection by Virulent and Avirulent Mycobacteria Reveals a Distinct Role of the Cytosolic RNA Sensor RIG-I in Mycobacterium tuberculosis Pathogenesis.

Choudhary Eira E Bullen C Korin CK Goel Renu R Singh Alok Kumar AK Praharaj Monali M Thakur Preeti P Dhiman Rohan R Bishai William R WR Agarwal Nisheeth N

Journal of proteome research 20200514 6

Comparative phosphoproteomics of Mycobacterium tuberculosis (Mtb)- and Mycobacterium bovis BCG (BCG)-infected macrophages could be instrumental in understanding the characteristic post-translational modifications of host proteins and their subsequent involvement in determining Mtb pathogenesis. To identify proteins acquiring a distinct phosphorylation status, herein, we compared the phosphorylation profile of macrophages upon exposure to Mtb and BCG. We observed a significant depho ...[more]

PMID: 32407090

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Transcriptome analysis of the Tap efflux pump mutant in Mycobacterium bovis BCG.

Project description:We used DNA microarrays to define the physiological roles of the Tap efflux pump in M. bovis BCG during the exponential and the stationary phase of in vitro growth. For this purpose we constructed a M. bovis BCG strain in which the tap gene was inactivated by the insertion of a hygromycin resistance cassette (?-hyg). When the gene expression patterns of the tap mutant were compared to the wild-type strain, almost no differences were observed during exponential growth; only seven genes slightly increased their expression. In contrast, more that 100 genes showed a variation in their level of expression during stationary growth. More than ten representative genes were chosen from the microarray experiments and their expression was measured by quantitative RT-PCR using sigA as invariant internal control. In support to the gene expression profiling data, the mRNA levels of all selected genes was significantly different in the tap mutant strain relative to control. A functional category analysis (http://tuberculist.epfl.ch/index.html) of the genes differentially expressed revealed a high proportion belonging to the Virulence, Detoxification, Adaptation (VDA), Intermediary Metabolism and Respiration (IMR), Conserved Hypotheticals (CH), and Cell Wall and Cell Processing (CWCP) categories suggesting a major adaptation to a stress generated by inactivation of the tap efflux pump gene. We compared the global gene expression of the tap mutant versus the wild-type strain of M. bovis BCG during the exponential (one week; OD540= 0.2-0.3) and stationary (six weeks; OD540= 0.8-1.0) growth. Hybridizations were performed using RNA extracted from two different biological samples. Each sample was hybridized twice through swap labeling of the respective cDNAs.

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A Ferritin Mutant Induces Protective Immunity against Virulent Mycobacterium tuberculosis Infection

Project description:Iron plays a critical role in the pathogenesis of many organisms including Mtb. It is the preferred redox cofactor in many basic cellular processes but due to its insolubility and potential toxicity under physiological conditions is a limiting nutrient in the host environment. Previously, we demonstrated that Mtb requires the iron storage protein ferritin (BfrB), for adaptation to both low and sufficient concentrations of environmental iron. We also showed that absence of bfrB compromises the ability of Mtb to overcome iron deficiency and prevent excess iron toxicity. In this study, we tested whether vaccination with ?bfrB could elicit host protective immune response against virulent Mtb infection. The results show that immunization of mice with the ?bfrB stimulates protective immunity associated with reduced immunopathology and better containment of the infection compared to vaccination with BCG. Genome-wide transcriptome analysis showed a distinct expression pattern of significantly differentially expressed genes (SDEG) between the ?bfrB and BCG-vaccinated, Mtb-infected mice lungs. Our network/pathway analysis of SDEG revealed significant inhibition of inflammatory response genes and activation of fibrosis genes in the ?bfrB, compared to BCG vaccinated, Mtb-infected mice lungs. The results provide a frame work for the study of mechanisms of protection relevant for the design of new and improved preventive strategies for TB. Female C57BL/6 mice were vaccinated subcutaneously with ?bfrB or BCG . At 8 weeks post-vaccination, mice were aerosol infected with Mtb H37Rv. At 4 weeks post infection, mice were sacrificed and lungs were removed. Lung total RNA from vaccinated and Mtb-infected mice was extracted, purified and were processed separately for microarray analysis.

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