Mycobacterium ulcerans mycolactones-fungi crosstalking

Hammoudi, Nassim; Cassagne, Carole; Armstrong, Nicholas; Ranque, Stéphane; Henrissat, Bernard; Drancourt, Michel; Bouam, Amar

doi:10.1038/s41598-019-39927-3

Cited by 7 publications

(12 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The novelty in our study was to find significant, antiparallel associations between M. ulcerans and fungi: M. ulcerans was detected on the skin along with Aspergillus , in which spore germination and the fungal network were stimulated by mycolactones, whereas the detection of M. ulcerans has never been associated with the the presence of Penicillium species in the skin, Accordingly, spore germination of P. rubens was inhibited by mycolactones. Therefore, our clinical observations were not fortuitous but revealed transkingdom mycobacteria-fungi interactions, supporting preliminary observations made with the Zygomycete Mucor circinelloides [26]. Of note, the transkingdom communication concerned P. rubens , a penicillin-producing strain, alias P. chrysogenum , made famous by Sir Alexandre Fleming [33].…”

Section: Discussionsupporting

confidence: 85%

See 1 more Smart Citation

Investigation of skin microbiota reveals Mycobacterium ulcerans-Aspergillus sp. trans-kingdom communication

Hammoudi

Cassagne

Million

et al. 2019

Preprint

View full text Add to dashboard Cite

BackgroundMycobacterium 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 findingsIn 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.ConclusionThese 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 summaryBuruli 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.

show abstract

Section: Discussionsupporting

confidence: 85%

“…On the other hand, fungal spores were put in Sabouraud liquid medium containing 20uL of mycolactones AB / C or 20uL of PBS as a negative control. The effect of Mycolactone AB/C on spore germination was then monitored as previously described [26].…”

Section: Methodsmentioning

confidence: 99%

Investigation of skin microbiota reveals Mycobacterium ulcerans-Aspergillus sp. trans-kingdom communication

Hammoudi

Cassagne

Million

et al. 2019

Preprint

View full text Add to dashboard Cite

show abstract

“…1). Mycolactone has also been found to enhance spore germination and chemoattractant effects on some fungal species [15]. This may explain the reason for fungal detection in BU lesions as well as the major contaminant for MU culture.…”

Section: Discussionmentioning

confidence: 98%

“…Even though mycolactone was initially thought to inhibit the growth of other bacteria on BU lesions, recent reports have identified secondary bacterial infections of BU wounds in both pre-treatment, during treatment, and post treatment [10,13,14]. Few studies have highlighted fungal element associated with BU [15]. There is, albeit insufficient information on the effect of antibiotics on secondary microorganism present in BU wounds.…”

Section: Introductionmentioning

confidence: 99%

Microbiology of secondary infections in Buruli ulcer lesions; implications for therapeutic interventions

et al. 2021

View full text Add to dashboard Cite

Background Buruli ulcer (BU) is a skin disease caused by Mycobacterium ulcerans and is the second most common mycobacterial disease after tuberculosis in Ghana and Côte d’Ivoire. M. ulcerans produces mycolactone, an immunosuppressant macrolide toxin, responsible for the characteristic painless nature of the infection. Secondary infection of ulcers before, during and after treatment has been associated with delayed wound healing and resistance to streptomycin and rifampicin. However, not much is known of the bacteria causing these infections as well as antimicrobial drugs for treating the secondary microorganism. This study sought to identify secondary microbial infections in BU lesions and to determine their levels of antibiotic resistance due to the prolonged antibiotic therapy required for Buruli ulcer. Results Swabs from fifty-one suspected BU cases were sampled in the Amansie Central District from St. Peters Hospital (Jacobu) and through an active case surveillance. Forty of the samples were M. ulcerans (BU) positive. Secondary bacteria were identified in all sampled lesions (N = 51). The predominant bacteria identified in both BU and Non-BU groups were Staphylococci spp and Bacilli spp. The most diverse secondary bacteria were detected among BU patients who were not yet on antibiotic treatment. Fungal species identified were Candida spp, Penicillium spp and Trichodema spp. Selected secondary bacteria isolates were all susceptible to clarithromycin and amikacin among both BU and Non-BU patients. Majority, however, had high resistance to streptomycin. Conclusions Microorganisms other than M. ulcerans colonize and proliferate on BU lesions. Secondary microorganisms of BU wounds were mainly Staphylococcus spp, Bacillus spp and Pseudomonas spp. These secondary microorganisms were less predominant in BU patients under treatment compared to those without treatment. The delay in healing that are experienced by some BU patients could be as a result of these bacteria and fungi colonizing and proliferating in BU lesions. Clarithromycin and amikacin are likely suitable drugs for clearance of secondary infection of Buruli ulcer.

show abstract

“…The specific function of mycolactone in nature remains unclear. Mycolactone is known to be a major virulence factor causing the human skin ulcers characteristics of BU disease [22,23], as key in the colonization of the salivary glands of water bugs (family Naucoridae) in laboratory conditions [24] and as a potential fungal chemoattractant [25]. It seems plausible that the expression of the virulence genes might be associated with stress conditions, as the colonization of new habitats such as the subdermal layer of human skin or salivary glands in water bugs.…”

Section: Discussionmentioning

confidence: 99%

Environmental Variations in Mycobacterium ulcerans Transcriptome: Absence of Mycolactone Expression in Suboptimal Environments

Sanhueza

Guégan

Jordan

et al. 2019

Toxins

View full text Add to dashboard Cite

Buruli ulcer is a neglected tropical infectious disease, produced by the environmentally persistent pathogen Mycobacterium ulcerans (MU). Neither the ecological niche nor the exact mode of transmission of MU are completely elucidated. However, some environmental factors, such as the concentration in chitin and pH values, were reported to promote MU growth in vitro. We pursued this research using next generation sequencing (NGS) and mRNA sequencing to investigate potential changes in MU genomic expression profiles across in vitro environmental conditions known to be suitable for MU growth. Supplementing the growth culture medium in either chitin alone, calcium alone, or in both chitin and calcium significantly impacted the MU transcriptome and thus several metabolic pathways, such as, for instance, those involved in DNA synthesis or cell wall production. By contrast, some genes carried by the virulence plasmid and necessary for the production of the mycolactone toxin were expressed neither in control nor in any modified environments. We hypothesized that these genes are only expressed in stressful conditions. Our results describe important environmental determinants playing a role in the pathogenicity of MU, helping the understanding of its complex natural life cycle and encouraging further research using genomic approaches.

show abstract

Mycobacterium ulcerans mycolactones-fungi crosstalking

Cited by 7 publications

References 35 publications

Investigation of skin microbiota reveals Mycobacterium ulcerans-Aspergillus sp. trans-kingdom communication

Investigation of skin microbiota reveals Mycobacterium ulcerans-Aspergillus sp. trans-kingdom communication

Microbiology of secondary infections in Buruli ulcer lesions; implications for therapeutic interventions

Environmental Variations in Mycobacterium ulcerans Transcriptome: Absence of Mycolactone Expression in Suboptimal Environments

Contact Info

Product

Resources

About