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Mycobacterium ulcerans Experimental Dormancy

Ahmed LoukilAix Marseille Univ., IRD, APHM, MEPHI, Marseille, France;

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Rym LalaouiAix Marseille Univ., IRD, APHM, MEPHI, Marseille, France;
IHU-Méditerranée Infection, Marseille, France;

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Hervé BogreauIHU-Méditerranée Infection, Marseille, France;
Unité Parasitologie et Entomologie, Département Microbiologie et Maladies Infectieuses, Institut de Recherche Biomédicale des Armées, IHU Méditerranée Infection, Marseille, France;
Aix Marseille Univ., IRD, SSA, AP-HM, VITROME, Marseille, France

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Sofiane RegouiIHU-Méditerranée Infection, Marseille, France;

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Michel DrancourtAix Marseille Univ., IRD, APHM, MEPHI, Marseille, France;
IHU-Méditerranée Infection, Marseille, France;

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Nassim HammoudiAix Marseille Univ., IRD, APHM, MEPHI, Marseille, France;
IHU-Méditerranée Infection, Marseille, France;

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ABSTRACT.

Whether Mycobacterium ulcerans, the etiological agent of Buruli ulcer in numerous tropical countries, would exist in a dormant state as reported for closely related Mycobacterium species, has not been established. Six M. ulcerans strains were exposed to a progressive depletion in oxygen for 2 months, using the Wayne model of dormancy previously described for M. tuberculosis, and further examined by microscopy after staining of dynamic, dormant, and dead mycobacteria (DDD staining), microcalorimetry and subculture in the presence of dead and replicative M. ulcerans as controls. Mycobacterium ulcerans CU001 strain died during the progressive oxygen depletion and four of five remaining strains exhibited Nile red–stained intracellular lipid droplets and a 14- to 20-day regrowth when exposed to ambient air, consistent with dormancy. A fifth M. ulcerans 19423 strain stained negative in DDD staining and slowly regrew in 27 days. Three tested M. ulcerans strains yielded microcalorimetric pattern similar to that of the negative (dead) homologous controls, differing from that of the homologous positive (replicative) controls. The relevance of these experimental observations, suggesting a previously unreported dormancy state of M. ulcerans, warrants further investigations in the natural ecological niches where M. ulcerans thrive as well as in Buruli ulcer lesions.

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Author Notes

Address correspondence to Michel Drancourt, MEPHI, IHU Méditerranée Infection, 27 Boulevard Jean Moulin, 13385 Marseille, France. E-mail: michel.drancourt@univ-amu.fr

Financial support: This study was supported by the Institut Hospitalo-Universitaire (IHU) Méditerranée Infection, the National Research Agency under the program « Investissements d’avenir », reference (ANR-10-IAHU-03).

Authors’ addresses: Ahmed Loukil, Aix Marseille Univ., IRD, APHM, MEPHI, Marseille, France, E-mail: loukilahmed@hotmail.com. Rym Lalaoui, Michel Drancourt, and Nassim Hammoudi, Aix Marseille Univ., IRD, APHM, MEPHI, Marseille, France, and IHU-Méditerranée Infection, Marseille, France, E-mails: l.rym-microbio@hotmail.fr, michel.drancourt@univ-amu.fr, and nassimveto15@live.fr. Hervé Bogreau, IHU-Méditerranée Infection, Marseille, France, Unité Parasitologie et Entomologie, Département Microbiologie et Maladies Infectieuses, Institut de Recherche Biomédicale des Armées, IHU Méditerranée Infection, Marseille, France, and Aix Marseille Univ., IRD, SSA, AP-HM, VITROME, Marseille, France, E-mail: hervebogreau@yahoo.fr. Sofiane Regoui, IHU-Méditerranée Infection, Marseille, France, E-mail: regoui.sofiane@gmail.com.

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