Correction: Whole Genome Comparisons Suggest Random Distribution of Mycobacterium ulcerans Genotypes in a Buruli Ulcer Endemic Region of Ghana

Background Buruli ulcer is a neglected tropical disease caused by Mycobacterium ulcerans, an environmental mycobacterium. Although transmission of M. ulcerans remains poorly understood, the main identified risk factor for acquiring Buruli ulcer is living in proximity of potentially contaminated water sources. Knowledge about the clinical features of Buruli ulcer and its physiopathology is increasing, but little is known about recurrence due to reinfection. Methodology/Principal findings We describe two patients with Buruli ulcer recurrence due to reinfection with M. ulcerans, as demonstrated by comparisons of DNA from the strains isolated at the time of the first diagnosis and at recurrence. Based on the spatial distribution of M. ulcerans genotypes in this region and a detailed study of the behavior of these two patients with respect to sources of water as well as water bodies and streams, we formulated hypotheses concerning the sites at which they may have been contaminated. Conclusions/Significance Second episodes of Buruli ulcer may occur through reinfection, relapse or a paradoxical reaction. We formally demonstrated that the recurrence in these two patients was due to reinfection. Based on the sites at which the patients reported engaging in activities relating to water, we were able to identify possible sites of contamination. Our findings indicate that the non-random distribution of M. ulcerans genotypes in this region may provide useful information about activities at risk.

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Single Nucleotide Polymorphism Typing of Mycobacterium ulcerans Reveals Focal Transmission of Buruli Ulcer in a Highly Endemic Region of Ghana

PLoS Neglected Tropical Diseases ◽

10.1371/journal.pntd.0000751 ◽

2010 ◽

Vol 4 (7) ◽

pp. e751 ◽

Cited By ~ 37

Author(s):

Katharina Röltgen ◽

Weihong Qi ◽

Marie-Thérèse Ruf ◽

Ernestina Mensah-Quainoo ◽

Sacha J. Pidot ◽

...

Keyword(s):

Single Nucleotide Polymorphism ◽

Buruli Ulcer ◽

Mycobacterium Ulcerans ◽

Nucleotide Polymorphism ◽

Endemic Region ◽

Single Nucleotide ◽

Single Nucleotide Polymorphism Typing

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Geographic microevolution of Mycobacterium ulcerans sustains Buruli ulcer extension, Australia

10.1101/2020.11.03.366435 ◽

2020 ◽

Author(s):

Jamal Saad ◽

Nassim Hammoudi ◽

Rita Zgheib ◽

Hussein Anani ◽

Michel Drancourt

Keyword(s):

Protein Gene ◽

Buruli Ulcer ◽

South Australia ◽

Mycobacterium Ulcerans ◽

Whole Genome ◽

Genome Sequences ◽

Specific Sequence ◽

Functional Studies ◽

Sequence Variations ◽

Family Protein

AbstractThe reason why severe cases of Buruli ulcers caused by Mycobacterium ulcerans are emerging in some South Australia counties has not been determined. In this study, we measured the diversity of M. ulcerans complex whole genome sequences (WGS) and reported a marker of this diversity. Using this marker as a probe, we compared WGS diversity in Buruli ulcer-epidemic South Australia counties versus non-epidemic Australian counties and further refined comparisons at the level of counties where severe Buruli ulcer cases have been reported. Analyzing 218 WGS (35 complete and 183 reconstructed WGS, including 174 Australian WGS) yielded 15 M. ulcerans complex genotypes, including three genotypes specific to Australia and one genotype specific to South Australia. A 1,068-bp PPE family protein gene exhibiting genotype-specific sequence variations was employed to further probe 13 minority clones hidden in sequence reads. The repartition of these clones significantly differed between South Australia and the rest of Australia. In addition, a significantly higher prevalence of 3/13 clones was observed in South Australia counties of the Mornington Peninsula, Melbourne and Bellarine Peninsula than in other South Australia counties. The data presented in this report suggest that the microevolution of three M. ulcerans complex clones drove the emergence of severe Buruli ulcer cases in some South Australia counties. Sequencing one specific PPE gene served to efficiently probe M. ulcerans complex clones. Further functional studies may balance the environmental adaptation and virulence of these clones.

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Whole-Genome Sequence of Mycobacterium ulcerans CSURP7741, a French Guianan Clinical Isolate

Microbiology Resource Announcements ◽

10.1128/mra.00215-19 ◽

2019 ◽

Vol 8 (29) ◽

Cited By ~ 1

Author(s):

Jamal Saad ◽

Marine Combe ◽

Nassim Hammoudi ◽

Pierre Couppié ◽

Romain Blaizot ◽

...

Keyword(s):

Clinical Isolate ◽

Genome Sequence ◽

Buruli Ulcer ◽

Gc Content ◽

Mycobacterium Ulcerans ◽

Whole Genome Sequence ◽

Whole Genome ◽

Protein Coding ◽

Content Type ◽

Rna Genes

Combined Nanopore and Illumina whole-genome sequencing of a French Guianan Mycobacterium ulcerans (Buruli ulcer agent) clinical isolate yielded a 5.12-Mbp genome with a 65.5% GC content, 5,215 protein-coding genes, and 51 predicted RNA genes. This publicly available M. ulcerans whole-genome sequence from a strain isolated in South America is closely related to M. ulcerans subsp. liflandii.

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Case Report: A New Mycobacterium ulcerans Genotype Causing Buruli Ulcer in Côte d’Ivoire

American Journal of Tropical Medicine and Hygiene ◽

10.4269/ajtmh.20-1307 ◽

2021 ◽

Author(s):

Philippe Bahadoran ◽

Nassim Hammoudi ◽

Alice Gaudart ◽

Jamal Saad ◽

Yoan Di Filippo ◽

...

Keyword(s):

Case Report ◽

Cote D'ivoire ◽

Côte D’Ivoire ◽

Buruli Ulcer ◽

Opportunistic Pathogen ◽

Mycobacterium Ulcerans ◽

Rural Populations ◽

Whole Genome ◽

Cote D’Ivoire ◽

Côte D'ivoire

Mycobacterium ulcerans, the opportunistic pathogen causing Buruli ulcer, is reported to affect rural populations in 36 tropical countries. We report one case of Buruli ulcer in a peri-urban area in Côte d’Ivoire, confirmed by whole genome sequencing which indicated a M. ulcerans genotype previously unreported in Côte d’Ivoire.

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

10.1101/869636 ◽

2019 ◽

Cited By ~ 1

Author(s):

N. Hammoudi ◽

C Cassagne ◽

M. Million ◽

S Ranque ◽

O. Kabore ◽

...

Keyword(s):

Burkina Faso ◽

Aspergillus Flavus ◽

Dna Sequences ◽

Buruli Ulcer ◽

Opportunistic Pathogen ◽

Negative Control ◽

Mycobacterium Ulcerans ◽

Skin Microbiota ◽

Endemic Region

ABSTRACTBackgroundMycobacterium 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.

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First Molecular Characterisation of Clinical Strains of Mycobacterium ulcerans in Togo (West Africa)

Microbiology Research Journal International ◽

10.9734/mrji/2018/v26i530076 ◽

2019 ◽

pp. 1-14

Author(s):

Menssah Teko ◽

Mounerou Salou ◽

Solange E. Kakou Ngazoa ◽

Issaka Maman ◽

Kodjovi Agbodeka ◽

...

Keyword(s):

West Africa ◽

Tandem Repeats ◽

Buruli Ulcer ◽

Variable Number ◽

Mycobacterium Ulcerans ◽

Clinical Samples ◽

Molecular Technique ◽

Endemic Region ◽

Typing Method ◽

Genetic Strains

Background: Buruli ulcer is the third most common mycobacterial disease worldwide. Cases most occur in 30 countries but severe cases occur in West Africa countries such as Benin, Cote d’Ivoire and Togo mainly in rural regions. Early diagnosis may prevent severe disability. The molecular technique seems the best solution and new Mycobacterial Interspersed Repetitive Units (MIRU) and variable number tandem repeats (VNTR) typing method are themost reproducible in this regard. They propose geographical, inter and intraspecies differentiation and can be used as a diagnosis tool. Objective: The objective of this study was to investigate the molecular diversity by using MIRUVNTR typing in clinical samples of BU patients in Togo. Study Design: 64 DNA extracts from clinical samples were collected from BU patients in the two principal endemics districts in Togo (Yoto and Zio) with three less endemic districts (Bas Mono, Lacs and Vo). First, IS2404 and KR real-time PCR plus IS2606 conventional PCR were performed. In a second step, the strains were analysed by PCR typing for five specific and sensitive markers MIRU1, VNTR6, ST1, VNTR19 and VNTR9. Results and Conclusion: 71.11% were positive for IS2404, 3.13% were positives for PCR-KR and 31.11% for IS 2606. By MIRU-VNTR typing, 48.86% positive result was found for MIRU1 and 25.00%, 20.31%, 18.75% and 14.06% for VNTR6, ST1, VNTR19 and VNTR9 respectively. One of the samples was negative for all genotyping markers. Two different genetic profiles were identified by MIRU1, ST1 and VNTR loci by gel-analysed of the amplified products. The VNTR profile B (3,1,1,2) corresponding of 3 copies MIRU1, 1 copy VNTR6, 1 copy ST-1 and two copies of VNTR19 was detected in 15.63% of samples and the VNTR profile A (1,1,1,2) corresponding of 1 copy MIRU1, 1 copy VNTR6, 1 copy ST-1 and 2 copies of VNTR19 was detected in 3.13% of samples and confirms the West African genotype (3,1,1) in Togo. Different genetic strains of Mycobacterium ulcerans (M. ulcerans) were co-circulated in the same endemic region in the country. This study has described first the circulating of different genetic strains of M. ulcerans in Togo.

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

Scientific Reports ◽

10.1038/s41598-021-83236-7 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

N. Hammoudi ◽

C. Cassagne ◽

M. Million ◽

S. Ranque ◽

O. Kabore ◽

...

Keyword(s):

Dna Sequences ◽

Buruli Ulcer ◽

Opportunistic Pathogen ◽

Fungal Species ◽

Negative Control ◽

Mycobacterium Ulcerans ◽

Skin Microbiota ◽

Endemic Region ◽

Aspergillus Sp

AbstractMycobacterium 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. 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. 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.

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Interactions between ecological and socio-economic drivers of Buruli ulcer burden in Sub-Saharan Africa: opportunities for an improved control

10.1093/oso/9780198789833.003.0014 ◽

2018 ◽

Author(s):

Andes Garchitorena ◽

Matthew H. Bonds ◽

Jean-Francois Guégan ◽

Benjamin Roche

Keyword(s):

Socioeconomic Factors ◽

Disease Transmission ◽

Access To Health Care ◽

Buruli Ulcer ◽

Mycobacterium Ulcerans ◽

Sub Saharan Africa ◽

Aquatic Environments ◽

Human Populations ◽

Complex Interactions ◽

Sub Saharan

This chapter provides an overview of the complex interactions between ecological and socioeconomic factors for the development and control of Buruli ulcer in Sub-Saharan Africa. We review key ecological and evolutionary processes driving the environmental persistence and proliferation of Mycobacterium ulcerans, the causative agent, within aquatic environments, as well as transmission processes from these aquatic environments to human populations. We also outline key socioeconomic factors driving the economic and health burden of Buruli ulcer in endemic regions, revealed by reciprocal feedbacks between poverty, disease transmission from exposure aquatic environments and disease progression to severe stages owing to low access to health care. The implications of such insights for disease control, both in terms of limitations of current strategies and directions for the future, are discussed.

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