Nutritional markers and proteome in patients undergoing treatment for pulmonary tuberculosis differ by geographic region

Contemporary phase 2 TB disease treatment clinical trials have found that microbiologic treatment responses differ between African versus non-African regions, the reasons for which remain unclear. Understanding host and disease phenotypes that may vary by region is important for optimizing curative...

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Vydáno v:	PloS one Ročník 16; číslo 5; s. e0250586
Hlavní autoři:	Jarsberg, Leah G., Kedia, Komal, Wendler, Jason, Wright, Aaron T., Piehowski, Paul D., Gritsenko, Marina A., Shi, Tujin, Lewinsohn, David M., Sigal, George B., Weiner, Marc H., Smith, Richard D., Keane, Joseph, Jacobs, Jon M., Nahid, Payam
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	United States Public Library of Science 05.05.2021 Public Library of Science (PLoS)
Témata:	Adult Analysis Antiinfectives and antibacterials Antimicrobial activity BASIC BIOLOGICAL SCIENCES Bioengineering Biology and Life Sciences Biomarkers Biomarkers - metabolism Blood proteins Care and treatment Chemical engineering Clinical medicine Clinical trials Critical care Data analysis Dosage Drug metabolism Editing Ethambutol Female Funding Humans Informed consent Isoniazid Laboratories Lipid Metabolism Male Medicine Medicine and Health Sciences Metabolism Methodology Middle Aged Mycobacterium tuberculosis - drug effects Mycobacterium tuberculosis - isolation & purification Mycobacterium tuberculosis - metabolism North America Nutrition Nutritional Physiological Phenomena People and Places Pharmacodynamics Pharmacokinetics Pharmacology Physical sciences Population studies Product/Service Evaluations Proteome - metabolism Proteomes Proteomics - methods Pulmonary tuberculosis Pyrazinamide Review boards Rifampin South Africa Spain Treatment Outcome Tuberculosis Tuberculosis, Pulmonary - drug therapy Tuberculosis, Pulmonary - metabolism Tuberculosis, Pulmonary - microbiology Uganda Young Adult South Africa Uganda North America Spain Sub-Saharan Africa Oregon San Francisco California United States > US Texas Africa California Pacific Northwest
ISSN:	1932-6203, 1932-6203
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Popis
Shrnutí:	Contemporary phase 2 TB disease treatment clinical trials have found that microbiologic treatment responses differ between African versus non-African regions, the reasons for which remain unclear. Understanding host and disease phenotypes that may vary by region is important for optimizing curative treatments. We characterized clinical features and the serum proteome of phase 2 TB clinical trial participants undergoing treatment for smear positive, culture-confirmed TB, comparing host serum protein expression in clinical trial participants enrolled in African and Non-African regions. Serum samples were collected from 289 participants enrolled in the Centers for Disease Control and Prevention TBTC Study 29 (NCT00694629) at time of enrollment and at the end of the intensive phase (after 40 doses of TB treatment). After a peptide level proteome analysis utilizing a unique liquid chromatography IM-MS platform (LC-IM-MS) and subsequent statistical analysis, a total of 183 core proteins demonstrated significant differences at both baseline and at week 8 timepoints between participants enrolled from African and non-African regions. The majority of the differentially expressed proteins were upregulated in participants from the African region, and included acute phase proteins, mediators of inflammation, as well as coagulation and complement pathways. Downregulated proteins in the African population were primarily linked to nutritional status and lipid metabolism pathways. We have identified differentially expressed nutrition and lipid pathway proteins by geographic region in TB patients undergoing treatment for pulmonary tuberculosis, which appear to be associated with differential treatment responses. Future TB clinical trials should collect expanded measures of nutritional status and further evaluate the relationship between nutrition and microbiologic treatment response.
Bibliografie:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 ObjectType-Article-2 ObjectType-Feature-1 content type line 23 ObjectType-Undefined-3 USDOE AC05-76RL01830 PNNL-SA-156554 Competing Interests: The authors declare no competing interests in regard any relevant declarations relating to employment, consultancy, patents, products in development, or marketed products, including those authors currently affiliated with Merck & Co Inc. and Meso Scale Diagnostics.
ISSN:	1932-6203 1932-6203
DOI:	10.1371/journal.pone.0250586