Molecular and epidemiological characterization of recurrent Mycobacterium ulcerans infections in Benin

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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Microbiological and molecular characterization of environmental mycobacterium strains isolated from the Buruli ulcer endemic and non-endemic zones in Cte dIvoire

African Journal of Microbiology Research ◽

10.5897/ajmr2016.8267 ◽

2016 ◽

Vol 10 (40) ◽

pp. 1703-1710

Author(s):

N. Vakou Sabine ◽

Coulibaly-Kalpy Julien ◽

E. Kakou-Ngazoa Solange ◽

Aka N`guetta ◽

D. Coulibaly N`golo ◽

...

Keyword(s):

Molecular Characterization ◽

Buruli Ulcer ◽

Environmental Mycobacterium

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

PLoS Neglected Tropical Diseases ◽

10.1371/journal.pntd.0003681 ◽

2015 ◽

Vol 9 (3) ◽

pp. e0003681 ◽

Cited By ~ 12

Author(s):

Anthony S. Ablordey ◽

Koen Vandelannoote ◽

Isaac A. Frimpong ◽

Evans K. Ahortor ◽

Nana Ama Amissah ◽

...

Keyword(s):

Random Distribution ◽

Buruli Ulcer ◽

Mycobacterium Ulcerans ◽

Whole Genome ◽

Endemic Region ◽

Genome Comparisons

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Molecular characterization of Mycobacterium ulcerans DNA gyrase and identification of mutations reduced susceptibility against quinolones in vitro

10.1101/2021.09.29.462499 ◽

2021 ◽

Author(s):

Hyun Kim ◽

Shigtarou Mori ◽

Tsuyoshi Kenri ◽

Yasuhiko Suzuki

Keyword(s):

Buruli Ulcer ◽

Dna Gyrase ◽

Resistance Mechanisms ◽

Docking Studies ◽

Mycobacterium Ulcerans ◽

Amino Acid Residues ◽

Wild Type Enzyme ◽

Ulcer Disease

ABSTRACTBuruli ulcer disease is a neglected necrotizing and disabling cutaneous tropical illness caused by Mycobacterium ulcerans (Mul). Fluoroquinolone (FQ), used in the treatment of this disease, has been known to act by inhibiting the enzymatic activities of DNA gyrase; however, the detailed molecular basis of these characteristics and the FQ resistance mechanisms in Mul remains unknown. This study investigated the detailed molecular mechanism of Mul DNA gyrase and the contribution of FQ resistance in vitro using recombinant proteins from the Mul subsp. shinshuense and Agy99 strains with reduced sensitivity to FQs. The IC50 of FQs against Ala91Vla and Asp95Gly mutants of Mul shinshuense and Agy99 GyrA subunits were 3.7- to 42.0-fold higher than those against wild-type enzyme. Similarly, the CC25 was 10- to 210-fold higher than those for the WT enzyme. Furthermore, the interaction between the amino acid residues of WT/mutant Mul DNA gyrase and FQ side chains was assessed via molecular docking studies. This is the first detailed study showing the contribution of Mul DNA GyrA subunit mutations to reduce the susceptibility against FQs.

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Identification of P218 as a Potent Inhibitor of Mycobacteria Ulcerans DHFR

10.26434/chemrxiv.12899420.v1 ◽

2020 ◽

Author(s):

Gustavo Pelicioli Riboldi ◽

Rachael Zigweid ◽

Peter J. Myler ◽

Stephen J. Mayclin ◽

Rafael Counago ◽

...

Keyword(s):

Chronic Disease ◽

Side Effects ◽

Dihydrofolate Reductase ◽

De Novo ◽

Potent Inhibitor ◽

Critical Role ◽

Buruli Ulcer ◽

Mycobacterium Ulcerans ◽

De Novo Biosynthesis

Mycobacterium ulcerans is the causative agent of Buruli ulcer, a debilitating chronic disease that mainly affects the skin. Current treatments for Buruli ulcer are efficacious, but rely on the use of antibiotics with severe side effects. The enzyme dihydrofolate reductase (DHFR) plays a critical role in the de novo biosynthesis of folate species and is a validated target for several antimicrobials. Here we describe the biochemical and structural characterization of M. ulcerans DHFR and identified P218, a safe antifolate compound in clinical evaluation for malaria, as a potent inhibitor of this enzyme. We expect our results to advance M. ulcerans DHFR as a target for future structure-based drug discovery campaigns.

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Characterization of the Molecular Lipophilicity of Mycolactones A/B and C, Infectious Factors of Mycobacterium ulcerans Agent of Buruli Ulcer

Chemical Science International Journal ◽

10.9734/csji/2021/v30i130211 ◽

2021 ◽

pp. 18-27

Author(s):

Kadjo François Kassi ◽

Jean Missa Ehouman ◽

Mamadou Guy-Richard Koné ◽

Lamoussa Ouattara ◽

Georges Stéphane Dembélé ◽

...

Keyword(s):

Biological Activities ◽

Subcutaneous Fat ◽

Buruli Ulcer ◽

Control Program ◽

Mycobacterium Ulcerans ◽

Key Factors ◽

Infected Area ◽

Very High

The work was undertaken as part of the Buruli ulcer control program. It is particularly about the determination of the lipophilicity of mycolactones A/B and C, infectious factors of Mycobacterium ulcerans, the agent of Buruli ulcer. The REKKER method and some free software such as MOLINSPIRATION, ACD/ChemSketch and EPIWED were used for the determination of the lipophilicity of mycolactones A/B and C. Very high logP values were found and respectively ranged from 12.11 to 11.41 for mycolactone A/B and 11.69 to 11.58 for mycolactone C. These values obtained from this coefficient, show that mycolactones A/B and C are naturally lipophilic and that actually reflects their effective presence in the subcutaneous fat of the infected area. These results are very encouraging and promising. They are key factors for a better understanding of the biological activities of the two mycolactones and pave the way for the proposal of a mechanism to annihilate their destructive effects.

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

PLoS Neglected Tropical Diseases ◽

10.1371/journal.pntd.0003798 ◽

2015 ◽

Vol 9 (5) ◽

pp. e0003798 ◽

Cited By ~ 1

Author(s):

Anthony S. Ablordey ◽

Koen Vandelannoote ◽

Isaac A. Frimpong ◽

Evans K. Ahortor ◽

Nana Ama Amissah ◽

...

Keyword(s):

Random Distribution ◽

Buruli Ulcer ◽

Mycobacterium Ulcerans ◽

Whole Genome ◽

Endemic Region ◽

Genome Comparisons

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Identification of P218 as a Potent Inhibitor of Mycobacteria Ulcerans DHFR

10.26434/chemrxiv.12899420 ◽

2020 ◽

Author(s):

Gustavo Pelicioli Riboldi ◽

Rachael Zigweid ◽

Peter J. Myler ◽

Stephen J. Mayclin ◽

Rafael Counago ◽

...

Keyword(s):

Chronic Disease ◽

Side Effects ◽

Dihydrofolate Reductase ◽

De Novo ◽

Potent Inhibitor ◽

Critical Role ◽

Buruli Ulcer ◽

Mycobacterium Ulcerans ◽

De Novo Biosynthesis

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Epidemiological Characterization of the Infection by Treponema Pallidum in Pregnant Women in Beira City, Sofala, Mozambique

Annals of Immunology & Immunotherapy ◽

10.23880/aii-16000123 ◽

2020 ◽

Vol 2 (2) ◽

Author(s):

Nchowela Guido

Keyword(s):

Pregnant Women ◽

Congenital Syphilis ◽

Health Centre ◽

Treponema Pallidum ◽

Timely Manner ◽

Pregnancy And Childbirth ◽

Epidemiological Characterization ◽

Active Syphilis ◽

Structured Questionnaire

Introduction: Syphilis is one of several diseases that can be transmitted during pregnancy and childbirth, which can lead to complications during pregnancy and in the newborn. This is especially so when the pregnant woman is not diagnosed or treated properly and in a timely manner. Methodology: Data from 262 pregnant women prospectively included, aged 18-41years, attended at the Ponta Gêa Health Centre for antenatal clinics has been analyzed from January to September of 2016. In the prospective study, a rapid treponemal and a non-treponemal test were performed. A structured questionnaire was used to collect socio demographic and clinical variables, which was developed from the literature review. Results: The prevalence of active syphilis was 11.8%; the majority of reactive pregnant women were aged 18-25years (55.4%), (61.3%) of pregnant women were treated with doses below those recommended; only a small number of the partners were treated successfully. The highest seroprevalence of syphilis was found in housewives (77%), in those who attended primary education (71.6%) in those who had a monthly income of 1000- 3000 MZN (70.3%), in those with two or more pregnancies (55.7%) and living with someone has husband and wife (63.5%). The syphilis/HIV co-infection rate was high. Conclusion: According to the results obtained in this study, urgent measures are needed to assess the problems encountered and to improve the screening approach, treatment and monitoring of syphilis during pregnancy in order to prevent the cases of congenital syphilis.

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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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