Case Report: A New Mycobacterium ulcerans Genotype Causing Buruli Ulcer in Cote d'Ivoire.
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ABSTRACT:
SUBMITTER: Bahadoran P
PROVIDER: S-EPMC8103442 | biostudies-literature | 2021 Apr
REPOSITORIES: biostudies-literature
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Case Report: A New Mycobacterium ulcerans Genotype Causing Buruli Ulcer in Côte d'Ivoire.
Bahadoran Philippe P Hammoudi Nassim N Gaudart Alice A Saad Jamal J Di Filippo Yoan Y Drancourt Michel M Ruimy Raymond R
The American journal of tropical medicine and hygiene 20210405 5
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. ...[more]
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Project description:Mycobacterium ulcerans, an environmental opportunistic pathogen, causes necrotic cutaneous and subcutaneous lesions, named Buruli ulcers, in tropical countries. PCR-derived tests used to detect M. ulcerans in environmental and clinical samples do not allow one-shot detection, identification, and typing of M. ulcerans among closely related Mycobacterium marinum complex mycobacteria. We established a 385-member M. marinum/M. ulcerans complex whole-genome sequence database by assembling and annotating 341 M. marinum/M. ulcerans complex genomes and added 44 M. marinum/M. ulcerans complex whole-genome sequences already deposited in the NCBI database. Pangenome, core genome, and single-nucleotide polymorphism (SNP) distance-based comparisons sorted the 385 strains into 10 M. ulcerans taxa and 13 M. marinum taxa, correlating with the geographic origin of strains. Aligning conserved genes identified one PPE (proline-proline-glutamate) gene sequence to be species and intraspecies specific, thereby genotyping the 23 M. marinum/M. ulcerans complex taxa. PCR sequencing of the PPE gene correctly genotyped nine M. marinum/M. ulcerans complex isolates among one M. marinum taxon and three M. ulcerans taxa in the African taxon (T2.4). Further, successful PPE gene PCR sequencing in 15/21 (71.4%) swabs collected from suspected Buruli ulcer lesions in Côte d'Ivoire exhibited positive M. ulcerans IS2404 real-time PCR and identified the M. ulcerans T2.4.1 genotype in eight swabs and M. ulcerans T2.4.1/T2.4.2 mixed genotypes in seven swabs. PPE gene sequencing could be used as a proxy for whole-genome sequencing for the one-shot detection, identification, and typing of clinical M. ulcerans strains, offering an unprecedented tool for identifying M. ulcerans mixed infections. IMPORTANCE We describe a new targeted sequencing approach that characterizes the PPE gene to disclose the simultaneous presence of different variants of a single pathogenic microorganism. This approach has direct implications on the understanding of pathogen diversity and natural history and potential therapeutic implications when dealing with obligate and opportunistic pathogens, such as Mycobacterium ulcerans presented here as a prototype.
| S-EPMC10269924 | biostudies-literature
Project description:Chronic tropical cutaneous ulcers remain a neglected medical condition in West Africa, particularly Buruli ulcer, which is caused by mycolactone cytotoxin-secreting Mycobacterium ulcerans (M. ulcerans). Medical management of this highly debilitating and necrotising skin infection may be modified by colonisation and co-infection of the ulcer by opportunistic and pathogenic microorganisms, which considerably delays and increases the cost of treatment. We diagnosed chronic tropical cutaneous ulcers in nine patients in Côte d'Ivoire using M. ulcerans-specific PCRs and culturomics. This revealed M. ulcerans in 7/9 ulcer swabs and 5/9 control swabs as well as an additional 122 bacterial species, 32 of which were specific to ulcers, 61 specifics to the controls, and 29 which were shared, adding 40 bacterial species to those previously reported. Whole genome sequencing of four Bordetella trematum (B. trematum) isolates in four Buruli ulcer swabs and no controls indicated cytolethal distending toxins, as confirmed by cytotoxic assay. In four cases of Buruli ulcer in Côte d'Ivoire, B. trematum was a co-pathogen which was resistant to rifampicin and clarithromycin, unmatching M. ulcerans antibiotic susceptibility profile and counteracting the current treatment of Buruli ulcer in West Africa and Australia. Thus, we report here chronic mixed M. ulcerans-B. trematum chronic tropical ulcer as a specific form of Buruli ulcer in West Africa.
| S-EPMC10703317 | biostudies-literature
Project description:Buruli ulcer (BU), a necrotic skin disease caused by Mycobacterium ulcerans, is mainly prevalent in West Africa, but cases have also been reported in other tropical parts of the world. It is the second most common mycobacterial disease after tuberculosis in Ghana and Côte d'Ivoire. Heterogeneity among M. ulcerans from different geographical locations has not been clearly elucidated, and some studies seem to suggest genetic differences between M. ulcerans in humans and in the environment. This study aimed at identifying genetic differences among M. ulcerans strains between two BU endemic countries: Ghana and Côte d'Ivoire. Clinical samples consisting of swabs, fine needle aspirates, and tissue biopsies of suspected BU lesions and environmental samples (e.g., water, biofilms from plants, soil, and detrital material) were analyzed. BU cases were confirmed via acid fast staining and PCR targeting the 16S rRNA, IS2404, IS2606, and ER domain genes present on M. ulcerans. Heterogeneity among M. ulcerans was determined through VNTR profiling targeting 10 loci. Eleven M. ulcerans genotypes were identified within the clinical samples in both Ghana and Côte d'Ivoire, whiles six M. ulcerans genotypes were found among the environmental samples. Clinical M. ulcerans genotypes C, D, F, and G were common in both countries. Genotype E was unique among the Ghanaian samples, whiles genotypes A, Z, J, and K were unique to the Ivorian samples. Environmental isolates were found to be more conserved compared with the clinical isolates. Genotype W was observed only among the Ghanaian environmental samples. Genotype D was found to be prominent in both clinical and environmental samples, suggesting evidence of possible transmission of M. ulcerans from the environment, particularly water bodies and biofilms from aquatic plants, to humans through open lesions on the skin.
| S-EPMC9262091 | biostudies-literature
Project description:BackgroundBuruli ulcer disease (BU), due to the bacteria Mycobacterium ulcerans, represents an important and emerging public health problem, especially in many African countries. Few elements are known nowadays about the routes of transmission of this environmental bacterium to the human population.Methodology/principal findingsIn this study, we have investigated the relationships between the incidence of BU in Côte d'Ivoire, western Africa, and a group of environmental variables. These environmental variables concern vegetation, crops (rice and banana), dams, and lakes. Using a geographical information system and multivariate analyses, we show a link between cases of BU and different environmental factors for the first time on a country-wide scale. As a result, irrigated rice field cultures areas, and, to a lesser extent, banana fields as well as areas in the vicinity of dams used for irrigation and aquaculture purposes, represent high-risk zones for the human population to contract BU in Côte d'Ivoire. This is much more relevant in the central part of the country.Conclusions/significanceAs already suspected by several case-control studies in different African countries, we strengthen in this work the identification of high-risk areas of BU on a national spatial scale. This first study should now be followed by many others in other countries and at a multi-year temporal scale. This goal implies a strong improvement in data collection and sharing in order to achieve to a global picture of the environmental conditions that drive BU emergence and persistence in human populations.
| S-EPMC2474700 | biostudies-literature
Project description: Not available
| S-EPMC6513118 | biostudies-literature
Project description:Buruli ulcer (BU) is an infectious skin disease caused by Mycobacterium ulcerans. It primarily affects disadvantaged rural populations and mainly impacts children who are chronically malnourished being especially vulnerable. In Côte d'Ivoire, the estimated prevalence of BU in children is 30 %. Malnutrition may further deteriorate the nutritional status of these individuals. This study aimed to compare the healing time of BU patients treated with the standard protocol (SP) of 8 weeks of rifampicin and clarithromycin combined with wound care versus those treated with the standard protocol plus nutritional support using Skin Renewal Medicine-1 (SPSRM-1) (UNHWA Medical Centre, Seoul, Republic of Korea). Additionally, the study measured the effects of SRM-1 on the patients' nutritional status. This was a prospective, randomized, single-blind paired interventional study conducted in BU-endemic health districts of Côte d'Ivoire. This 12-month study had two arms: the standard protocol versus the test treatment (SPSRM-1). SRM-1 is a cereal-based nutraceutical composed of 60 % cereal, 25 % vegetable, and 15 % plant concentrate. Patients included in the study had uncomplicated category I and II ulcerations without comorbidities. Nutritional status including haemoglobin, albumin levels, and body mass index (BMI) was evaluated from enrolment to the end of the study, alongside ulcer healing rates. Sixty BU wound patients were enrolled: 30 in the control group and 30 in the test group, with a mean age of 22 years. Of the patients, 28.3 % were malnourished, and 42 % had hypoalbuminemia. At the primary endpoint, 6 patients (20.0 %) in the SPSRM1 and 5 patients (16.7 %) in the SP group achieved complete epithelialization, with a reduction rate of 0.7 % per day in the SPSRM1 group compared to 0.3 % per day in the SP group. Patients who received SRM-1 had a higher BMI than those who did not, with a mean difference of 1.72 kg/m2 favouring the test group. Haemoglobin and albumin levels also showed improvement at the secondary endpoint compared to the control group. This study demonstrated the potential benefit of adding nutritional support to improve BU treatment outcomes, by shortening the healing time of ulcerations. However, further studies with larger sample sizes are necessary to confirm these findings.
| S-EPMC11607664 | biostudies-literature
Project description:Buruli ulcer (BU), a neglected tropical disease of the skin and subcutaneous tissue, is caused by Mycobacterium ulcerans and is the third most common mycobacterial disease after tuberculosis and leprosy. While there is a strong association of the occurrence of the disease with stagnant or slow flowing water bodies, the exact mode of transmission of BU is not clear. M. ulcerans has emerged from the environmental fish pathogen M. marinum by acquisition of a virulence plasmid encoding the enzymes required for the production of the cytotoxic macrolide toxin mycolactone, which is a key factor in the pathogenesis of BU. Comparative genomic studies have further shown extensive pseudogene formation and downsizing of the M. ulcerans genome, indicative for an adaptation to a more stable ecological niche. This has raised the question whether this pathogen is still present in water-associated environmental reservoirs. Here we show persistence of M. ulcerans specific DNA sequences over a period of more than two years at a water contact location of BU patients in an endemic village of Cameroon. At defined positions in a shallow water hole used by the villagers for washing and bathing, detritus remained consistently positive for M. ulcerans DNA. The observed mean real-time PCR Ct difference of 1.45 between the insertion sequences IS2606 and IS2404 indicated that lineage 3 M. ulcerans, which cause human disease, persisted in this environment after successful treatment of all local patients. Underwater decaying organic matter may therefore represent a reservoir of M. ulcerans for direct infection of skin lesions or vector-associated transmission.
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Project description:BACKGROUND: Mycobacterium ulcerans is an unusual bacterial pathogen with elusive origins. While closely related to the aquatic dwelling M. marinum, M. ulcerans has evolved the ability to produce the immunosuppressive polyketide toxin mycolactone and cause the neglected tropical disease Buruli ulcer. Other mycolactone-producing mycobacteria (MPM) have been identified in fish and frogs and given distinct species designations (M. pseudoshottsii, M. shinshuense, M. liflandii and M. marinum), however the evolution of M. ulcerans and its relationship to other MPM has not been defined. Here we report the comparative analysis of whole genome sequences from 30 MPM and five M. marinum. RESULTS: A high-resolution phylogeny based on genome-wide single nucleotide polymorphisms (SNPs) showed that M. ulcerans and all other MPM represent a single clonal group that evolved from a common M. marinum progenitor. The emergence of the MPM was driven by the acquisition of the pMUM plasmid encoding genes for the biosynthesis of mycolactones. This change was accompanied by the loss of at least 185 genes, with a significant overrepresentation of genes associated with cell wall functions. Cell wall associated genes also showed evidence of substantial adaptive selection, suggesting cell wall remodeling has been critical for the survival of MPM. Fine-grain analysis of the MPM complex revealed at least three distinct lineages, one of which comprised a highly clonal group, responsible for Buruli ulcer in Africa and Australia. This indicates relatively recent transfer of M. ulcerans between these continents, which represent the vast majority of the global Buruli ulcer burden. Our data provide SNPs and gene sequences that can differentiate M. ulcerans lineages, suitable for use in the diagnosis and surveillance of Buruli ulcer. CONCLUSIONS: M. ulcerans and all mycolactone-producing mycobacteria are specialized variants of a common Mycobacterium marinum progenitor that have adapted to live in restricted environments. Examination of genes lost or retained and now under selective pressure suggests these environments might be aerobic, and extracellular, where slow growth, production of an immune suppressor, cell wall remodeling, loss or modification of cell wall antigens, and biofilm-forming ability provide a survival advantage. These insights will guide our efforts to find the elusive reservoir(s) of M. ulcerans and to understand transmission of Buruli ulcer.
| S-EPMC3434033 | biostudies-literature
Project description:Buruli ulcer (BU) occurs in >30 countries. The causative organism, Mycobacterium ulcerans, is acquired from the environment, but the exact mode of transmission is unknown. We investigated an outbreak of BU in a small coastal town in southeastern Australia and screened by PCR mosquitoes caught there. All cases of BU were confirmed by culture or PCR. Mosquitoes were trapped in multiple locations during a 26-month period. BU developed in 48 residents of Point Lonsdale/Queenscliff and 31 visitors from January 2001 through April 2007. We tested 11,504 mosquitoes trapped at Point Lonsdale (predominantly Aedes camptorhynchus). Forty-eight pools (5 species) were positive for insertion sequence IS2404 (maximum likelihood estimate 4.3/1,000), and we confirmed the presence of M. ulcerans in a subset of pools by detection of 3 additional PCR targets.
| S-EPMC3375796 | biostudies-literature
Project description:Buruli ulcer is a noncontagious disabling cutaneous and subcutaneous mycobacteriosis reported by 33 countries in Africa, Asia, Oceania, and South America. The causative agent, Mycobacterium ulcerans, derives from Mycobacterium marinum by genomic reduction and acquisition of a plasmid-borne, nonribosomal cytotoxin mycolactone, the major virulence factor. M. ulcerans-specific sequences have been readily detected in aquatic environments in food chains involving small mammals. Skin contamination combined with any type of puncture, including insect bites, is the most plausible route of transmission, and skin temperature of <30°C significantly correlates with the topography of lesions. After 30 years of emergence and increasing prevalence between 1970 and 2010, mainly in Africa, factors related to ongoing decreasing prevalence in the same countries remain unexplained. Rapid diagnosis, including laboratory confirmation at the point of care, is mandatory in order to reduce delays in effective treatment. Parenteral and potentially toxic streptomycin-rifampin is to be replaced by oral clarithromycin or fluoroquinolone combined with rifampin. In the absence of proven effective primary prevention, avoiding skin contamination by means of clothing can be implemented in areas of endemicity. Buruli ulcer is a prototype of ecosystem pathology, illustrating the impact of human activities on the environment as a source for emerging tropical infectious diseases.
| S-EPMC5740976 | biostudies-literature