Antimicrobial activity of Mycobacteriophage D29 Lysin B during Mycobacterium ulcerans infection
Buruli Ulcer (BU) is a cutaneous disease caused by Mycobacterium ulcerans. The pathogenesis of BU is closely related to the secretion of the toxin mycolactone that induces extensive destruction of the skin and soft tissues. Although the World Health Organization recommends a combination of rifampicin and streptomycin for the treatment of BU, clinical management of advanced stages often requires extensive surgical resection of the infected tissue. 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 Gram-positive bacteria. Amongst Gram-positive bacteria, mycobacteria have an unusual outer membrane that is covalently attached to the mycolyl arabinogalactan-peptidoglycan complex. To overcome this additional barrier to phage-mediated lysis, some mycobacteriophages encode a lipolytic enzyme, Lysin B (Lys B). In this study, we demonstrated for the first time that recombinant Lys B displays lytic activity against M. ulcerans isolates. Moreover, using a mouse model of M. ulcerans footpad infection, we show that subcutaneous treatment with Lys B leads to a reduction in bacterial burdens, associated with IFN-γ 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..
| Medienart: |
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Preprint| Erscheinungsjahr: |
2020 |
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| Erschienen: |
2020 |
| Enthalten in: |
bioRxiv.org - (2020) vom: 18. Jan. Zur Gesamtaufnahme - year:2020 |
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| Sprache: |
Englisch |
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| Beteiligte Personen: |
Fraga, Alexandra G. [VerfasserIn] |
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| Links: |
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| doi: |
10.1101/507129 |
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| funding: |
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| PPN (Katalog-ID): |
XBI000420042 |
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| 245 | 1 | 0 | |a Antimicrobial activity of Mycobacteriophage D29 Lysin B during Mycobacterium ulcerans infection |
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| 520 | |a Buruli Ulcer (BU) is a cutaneous disease caused by Mycobacterium ulcerans. The pathogenesis of BU is closely related to the secretion of the toxin mycolactone that induces extensive destruction of the skin and soft tissues. Although the World Health Organization recommends a combination of rifampicin and streptomycin for the treatment of BU, clinical management of advanced stages often requires extensive surgical resection of the infected tissue. 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 Gram-positive bacteria. Amongst Gram-positive bacteria, mycobacteria have an unusual outer membrane that is covalently attached to the mycolyl arabinogalactan-peptidoglycan complex. To overcome this additional barrier to phage-mediated lysis, some mycobacteriophages encode a lipolytic enzyme, Lysin B (Lys B). In this study, we demonstrated for the first time that recombinant Lys B displays lytic activity against M. ulcerans isolates. Moreover, using a mouse model of M. ulcerans footpad infection, we show that subcutaneous treatment with Lys B leads to a reduction in bacterial burdens, associated with IFN-γ 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. | ||
| 700 | 1 | |a Trigo, Gabriela |e verfasserin |4 aut | |
| 700 | 1 | |a Dominguez, Juan |e verfasserin |4 aut | |
| 700 | 1 | |a Silva-Gomes, Rita |e verfasserin |4 aut | |
| 700 | 1 | |a Gonçalves, Carine M. |e verfasserin |4 aut | |
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| 700 | 1 | |a Castro, António G. |e verfasserin |4 aut | |
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