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- Title
Combined Inflammatory and Metabolic Defects Reflected by Reduced Serum Protein Levels in Patients with Buruli Ulcer Disease.
- Authors
Phillips, Richard O.; Sarfo, Fred S.; Landier, Jordi; Oldenburg, Reid; Frimpong, Michael; Wansbrough-Jones, Mark; Abass, Kabiru; Thompson, William; Forson, Mark; Fontanet, Arnaud; Niang, Fatoumata; Demangel, Caroline
- Abstract
Buruli ulcer is a skin disease caused by Mycobacterium ulcerans that is spreading in tropical countries, with major public health and economic implications in West Africa. Multi-analyte profiling of serum proteins in patients and endemic controls revealed that Buruli ulcer disease down-regulates the circulating levels of a large array of inflammatory mediators, without impacting on the leukocyte composition of peripheral blood. Notably, several proteins contributing to acute phase reaction, lipid metabolism, coagulation and tissue remodelling were also impacted. Their down-regulation was selective and persisted after the elimination of bacteria with antibiotic therapy. It involved proteins with various functions and origins, suggesting that M. ulcerans infection causes global and chronic defects in the host's protein metabolism. Accordingly, patients had reduced levels of total serum proteins and blood urea, in the absence of signs of malnutrition, or functional failure of liver or kidney. Interestingly, slow healers had deeper metabolic and coagulation defects at the start of antibiotic therapy. In addition to providing novel insight into Buruli ulcer pathogenesis, our study therefore identifies a unique proteomic signature for this disease. Author Summary: Buruli ulcer is a skin disease caused by inoculation of Mycobacterium ulcerans bacteria, which is emerging in tropical countries. Lesions typically start as nodules, which eventually open to form progressive, non-healing wounds. Although anti-mycobacterial antibiotics are efficient at stopping the infection, ulcers often persist after completion of treatment for reasons that remain unclear. In the present study, we performed a quantitative analysis of a large array of proteins circulating in peripheral blood, with the view to identifying biomarkers of disease progression and wound chronicity. We found that Buruli ulcer disease induces a unique signature of serum protein suppression that outlasts the elimination of bacteria. Interestingly, the initial levels of several of these proteins differed between fast and slow healers, suggesting an association with healing defects. Our results unravel an unexpected feature of Buruli ulcer disease and show that M. ulcerans infection has global and durable effects on the host's protein metabolism.
- Subjects
WEST Africa; BURULI ulcer; BLOOD proteins; ACUTE phase reaction; ACUTE phase proteins; SKIN diseases; SKIN ulcers
- Publication
PLoS Neglected Tropical Diseases, 2014, Vol 8, Issue 4, p1
- ISSN
1935-2727
- Publication type
Article
- DOI
10.1371/journal.pntd.0002786