Mycolactone Gene Expression Is Controlled by Strong SigA-Like Promoters with Utility in Studies of Mycobacterium ulcerans and Buruli Ulcer

Nicholas Tobias; Torsten Seemann; Sacha Pidot; Jessica Porter; Laurent Marsollier; Estelle Marion; Franck Letournel; Tasnim Zakir; Joseph Azuolas; John Wallace; Hui Hong; John Davies; Benjamin Howden; Paul Johnson; Grant Jenkin; Timothy Stinear

doi:10.1371/journal.pntd.0000553

Article dans une revue

Mycolactone Gene Expression Is Controlled by Strong SigA-Like Promoters with Utility in Studies of Mycobacterium ulcerans and Buruli Ulcer

Nicholas Tobias ¹ Torsten Seemann ² Sacha Pidot ³ Jessica Porter ³ Laurent Marsollier ⁴ Estelle Marion ⁴ Franck Letournel ⁵ Tasnim Zakir ² Joseph Azuolas ⁶ John Wallace ⁷ Hui Hong ⁸ John Davies ² Benjamin Howden ^{3, 9, 2} Paul Johnson ¹⁰ Grant Jenkin ¹¹ Timothy Stinear ²

1 Goethe-Universität Frankfurt am Main

2 Monash University [Clayton]

3 The Peter Doherty Institute for Infection and Immunity [Melbourne]

4 GEIHP - Groupe d'Étude des Interactions Hôte-Pathogène

5 MINT - Micro et Nanomédecines Translationnelles

6 NSW DPI - New South Wales Department of Primary Industries

7 School of Medicine - Departments of Physiology & Pharmacology, and Medicine [Calgary, Canada]

8 CSBC - Cambridge Systems Biology Centre & Department of Biochemistry

9 Austin Health

10 Nuffield Department of Surgery

11 Department of Infectious Diseases [Monash Health, Clayton]

Abstract :

Buruli ulcer (BU) is a serious skin infection of humans predominantly occurring in West and Central Africa. The disease is caused by infection with Mycobacterium ulcerans, a bacterium that produces an unusual toxin called mycolactone. There are many unanswered questions surrounding BU, particularly regarding the role of mycolactone in disease and how M. ulcerans is transmitted to humans. Here, we have partly addressed these questions by identifying genetic factors controlling the transcription of the mycolactone genes. Using a variety of experimental approaches, including green fluorescent protein (GFP) as a reporter of gene expression, we have identified strong promoters that drive transcription of the mycolactone genes in M. ulcerans. We then used our GFP reporters to produce highly fluorescent M. ulcerans-GFP that were readily visualized by microscopy. Mosquitoes have been proposed as a potential vector of M. ulcerans so we used M. ulcerans-GFP in feeding experiments with mosquito larvae. M. ulcerans-GFP accumulated within the insects, whereas other mycobacteria did not. This is the first report of the mycolactone gene promoters, and we have used our findings to develop M. ulcerans-GFP, a strain in which fluorescence and toxin gene expression are linked, thus providing a powerful tool for studying Buruli ulcer.

Type de document :

Article dans une revue

Domaine :

Sciences du Vivant [q-bio]

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https://hal.univ-angers.fr/hal-03134792
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Soumis le : lundi 8 février 2021 - 14:57:30
Dernière modification le : mercredi 19 janvier 2022 - 16:34:02
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