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Comparative proteomics of activated THP-1 cells infected with mycobacterium tuberculosis identifies putative clearance biomarkers for tuberculosis treatment
Kaewseekhao B. - ไม่ระบุหน่วยงาน
ชื่อเรื่อง (EN): Comparative proteomics of activated THP-1 cells infected with mycobacterium tuberculosis identifies putative clearance biomarkers for tuberculosis treatment
ผู้แต่ง / หัวหน้าโครงการ (EN): Kaewseekhao B.
บทคัดย่อ (EN): Biomarkers for determining clearance of Mycobacterium tuberculosis (Mtb) infection during anti-tuberculosis therapy or following exposure could facilitate enhanced monitoring and treatment.We screened for biomarkers indicating clearance of Mtb infection in vitro. A comparative proteomic analysis was performed using GeLC MSI/MS. Intracellular and secreted proteomes from activated THP-1 cells infected with the Mtb H37Rv strain (MOI = 1) and treated with isoniazid and rifampicin for 1 day (infection stage) and 5 days (clearance stage) were analyzed. Host proteins associated with early infection (n = 82), clearance (n = 121), sustained in both conditions (n = 34) and suppressed by infection (n = 46) were elucidated. Of the potential clearance markers, SSFA2 and CAECAM18 showed the highest and lowest protein intensities, respectively. A western blot of CAECAM18 validated the LC MS/MS result. For three clearance markers (SSFA2, PARP14 and PSME4), in vivo clinical validation was concordantly reported in previous patient cohorts. A network analysis revealed that clearance markers were enriched amongst four protein interaction networks centered on: (i) CD44/CCND1, (ii) IFN-β1/NF-κB, (iii) TP53/TGF-β and (iv) IFN- γ/CCL2. After infection, proteins associated with proliferation, and recruitment of immune cells appeared to be enriched possibly reflecting recruitment of defense mechanisms. Counteracting proteins (CASP3 vs. Akt and NF-κB vs. TP53) associated with apoptosis regulation and its networks were enriched among the early and sustained infection biomarkers, indicating host-pathogen competition. The BRCA1/2 network was suppressed during infection, suggesting that cell proliferation suppression is a feature of Mtb survival. Our study provides insights into the mechanisms of host-Mtb interaction by comparing the stages of infection clearance. The identified clearance biomarkers may be useful in monitoring tuberculosis treatment. ©2015 Kaewseekhao et al.
บทคัดย่อ: ไม่พบข้อมูลจากหน่วยงานต้นทาง
ภาษา (EN): en
เอกสารแนบ (EN): https://www.scopus.com/inward/record.uri?eid=2-s2.0-84941695656&doi=10.1371%2fjournal.pone.0134168&partnerID=40&md5=7c9a233b995a32a90b48e8fa3d907ec0
เผยแพร่โดย (EN): มหาวิทยาลัยมหิดล
คำสำคัญ (EN): Tuberculosis
เจ้าของลิขสิทธิ์ (EN): มหาวิทยาลัยมหิดล
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Comparative proteomics of activated THP-1 cells infected with mycobacterium tuberculosis identifies putative clearance biomarkers for tuberculosis treatment
Kaewseekhao B.
มหาวิทยาลัยมหิดล
ไม่ระบุวันที่เผยแพร่
Delay in treatment initiation and treatment outcomes among adult patients with multidrug-resistant tuberculosis at Yangon Regional Tuberculosis Centre, Myanmar: A retrospective study การพัฒนาชุดทดสอบ Multiplex PCR สำหรับจำแนกชนิดเชื้อ Mycobacterium bovis และMycobacterium tuberculosis การพัฒนาชุดทดสอบ Multiplex PCR สำหรับจำแนกชนิดเชื้อ Mycobacterium bovis และ Mycobacterium tuberculosis Bioinformatics tools and databases for whole genome sequence analysis of Mycobacterium tuberculosis Drug-resistant Mycobacterium tuberculosis and its genotypes isolated from an outbreak in western Thailand. Detection of Mycobacterium tuberculosis and Its Rifampicin Resistance by Automated Nucleic Acid Amplification Test Risk factors for multidrug-resistant tuberculosis among patients with pulmonary tuberculosis at the central chest institute of Thailand QuantiFERON-TB Gold In-Tube Test for Tuberculosis Prevention in HIV-Infected Patients Implementation of tuberculosis intensive case finding, isoniazid preventive therapy, and infection control ("Three I's") and HIV-tuberculosis service integration in lower income countries Genotyping of Mycobacterium tuberculosis by Spoligotyping การตรวจแยกสายพันธุ์เชื้อวัณโรคด้วยวิธี Spoligotyping
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