RT Journal Article
SR Electronic
T1 Investigation of skin microbiota reveals <em>Mycobacterium ulcerans</em>-<em>Aspergillus</em> sp. trans-kingdom communication
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 869636
DO 10.1101/869636
A1 N. Hammoudi
A1 C Cassagne
A1 M. Million
A1 S Ranque
A1 O. Kabore
A1 M. Drancourt
A1 D. Zingue
A1 A. Bouam
YR 2019
UL http://biorxiv.org/content/early/2019/12/10/869636.abstract
AB Background Mycobacterium ulcerans secrete a series of non-ribosomal-encoded toxins known as mycolactones that are responsible for causing a disabling ulceration of the skin and subcutaneous tissues named Buruli ulcer. The disease is the sole non-contagion among the three most common mycobacterial diseases in humans. Direct contact with contaminated wetlands is a risk factor for Buruli ulcer, responsible for M. ulcerans skin carriage before transcutaneous inoculation with this opportunistic pathogen.Methodology and principal findings In this study, we analysed the bacterial and fungal skin microbiota in individuals exposed to M. ulcerans in Burkina Faso. We showed that M. ulcerans-specific DNA sequences were detected on the unbreached skin of 6/52 (11.5%) asymptomatic farmers living in Sindou versus 0/52 (0%) of those living in the non-endemic region of Tenkodogo. Then, we cultured the skin microbiota of asymptomatic M. ulcerans carriers and negative control individuals, all living in the region of Sindou. A total of 84 different bacterial and fungal species were isolated, 21 from M. ulcerans-negative skin samples, 31 from M. ulcerans-positive samples and 32 from both. More specifically, Actinobacteria, Aspergillus niger and Aspergillus flavus were significantly associated with M. ulcerans skin carriage. We further observed that in vitro, mycolactones induced spore germination of A. flavus, attracting the fungal network.Conclusion These unprecedented observations suggest that interactions with fungi may modulate the outcome of M. ulcerans skin carriage, opening new venues to the understanding of Buruli ulcer pathology, prophylaxis and treatment of this still neglected tropical infection.Author summary Buruli ulcer is a chronic infectious disease caused by the environmental opportunistic pathogen Mycobacterium ulcerans which secretes an exotoxin responsible for its pathogenicity. The reservoir and sources of M. ulcerans in the environment remain elusive and its mode of transmission is unclear. To acquire M. ulcerans infection, at least two conditions must be met, viable bacteria and a skin lesion as demonstrated by experimental animal models. In this study, we showed that M. ulcerans specific DNA sequences could be detected on the healthy skin of asymptomatic farmers living in one region of Burkina Faso where Buruli ulcer cases had already been reported, but not in Buruli ulcer-free regions, suggesting skin carriage after contacts with environmental sources. We also investigated the skin microbiota of M. ulcerans carriers and found significant associations of some bacteria and fungi with skin carriage of M. ulcerans. These associations may due to the effect of mycolactones on some fungi species. As we showed previously with Mucor circinelloides and here with Aspergillus flavus.