Serum levels of neopterin during antimicrobial treatment for Mycobacterium ulcerans infection.
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ABSTRACT:
SUBMITTER: de Zeeuw J
PROVIDER: S-EPMC3771288 | biostudies-literature | 2013 Sep
REPOSITORIES: biostudies-literature
Publications
Serum levels of neopterin during antimicrobial treatment for Mycobacterium ulcerans infection.
de Zeeuw Janine J Duggirala Sridevi S Nienhuis Willemien A WA Abass K Mohammed KM Tuah Wilson W Omansen Till F TF van der Werf Tjip S TS Stienstra Ymkje Y
The American journal of tropical medicine and hygiene 20130708 3
Neopterin is closely associated with activation of the cellular immune system. Neopterin levels differed between controls and patients with Buruli ulcer disease. No differences between patients with or without paradoxical responses were observed. Therefore, neopterin has no value in detecting paradoxical responses among patients with limited Buruli ulcer disease. Neopterin levels were lower in patients receiving clarithromycin. This finding might indicate a slower cellular immune recovery, with ...[more]
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Project description:Buruli Ulcer (BU) is a cutaneous disease caused by Mycobacterium ulcerans. The pathogenesis of this disease is closely related to the secretion of the toxin mycolactone that induces extensive destruction of the skin and soft tissues. Currently, there are no effective measures to prevent the disease and, despite availability of antibiotherapy and surgical treatments, these therapeutic options are often associated with severe side effects. Therefore, it is important to develop alternative strategies for the treatment of BU. Endolysins (lysins) are phage encoded enzymes that degrade peptidoglycan of bacterial cell walls. Over the past years, lysins have been emerging as alternative antimicrobial agents against bacterial infections. However, mycobacteria have an unusual outer membrane composed of mycolylarabinogalactan-peptidoglycan. To overcome this complex barrier, some mycobacteriophages encode a lipolytic enzyme, Lysin B (LysB). In this study, we demonstrate for the first time that recombinant LysB displays lytic activity against M. ulcerans isolates. Moreover, using a mouse model of M. ulcerans footpad infection, we show that subcutaneous treatment with LysB prevented further bacterial proliferation, associated with IFN-? and TNF production in the draining lymph node. These findings highlight the potential use of lysins as a novel therapeutic approach against this neglected tropical disease.
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