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Article ; Online: Impact of ceftriaxone and temocillin on fecal abundance of extended-spectrum β-lactamase producing Escherichia coli in a mouse model.

Rachel Chenouard / Rafael Mahieu / David Luque Paz / Estelle Marion / Matthieu Eveillard / Vincent Dubée

PLoS ONE, Vol 16, Iss 3, p e

2021 Volume 0248177

Abstract: Background Gut colonization by ESBL-producing Enterobacteriaceae (ESBL-PE) is widespread and is promoted by antibiotic exposure. Higher fecal abundance of ESBL-PE promotes the dissemination of the bacteria in the environment and is associated with ... ...

Abstract	Background Gut colonization by ESBL-producing Enterobacteriaceae (ESBL-PE) is widespread and is promoted by antibiotic exposure. Higher fecal abundance of ESBL-PE promotes the dissemination of the bacteria in the environment and is associated with increased risk of infection. Ceftriaxone and temocillin are commonly used antibiotics with a different activity on gut flora. Their impact on fecal abundance of ESBL-producing Enterobacteriaceae has not been studied. The objective of this study was to compare the propensity of ceftriaxone and temocillin to modify the abundance of ESBL-producing Escherichia coli in feces of colonized mice. Methods Mice received broad-spectrum antibiotics in order to disrupt their normal gut flora. A CTX-M-type ESBL-producing E. coli clinical isolate was then administered orally, leading to durable colonization. Thirty days later, mice received either temocillin or ceftriaxone with drinking water at a concentration simulating human intestinal exposure. Third-generation-cephalosporin resistant (3GCR) E. coli were enumerated in feces on selective medium before, 2 days and 10 days after the end of antibiotic exposure. The experiment was performed with two E. coli isolates with different temocillin minimum inhibitory concentrations. Results Exposure to ceftriaxone induced an increase in the fecal abundance of 3GCR E. coli. In contrast, temocillin had no effect or transiently decreased the number of 3GCR E. coli. Results obtained with the two strains were similar. Conclusion Contrary to ceftriaxone, temocillin does not promote expansion of ESBL-producing E. coli in feces of colonized mice. Thus temocillin may be a therapeutic of choice when a temocillin-susceptible strain infection is suspected or proven to prevent the expansion of ESBL-PE in a previously colonized patient.
Keywords	Medicine ; R ; Science ; Q
Language	English
Publishing date	2021-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: A combined field study of Buruli ulcer disease in southeast Benin proposing preventive strategies based on epidemiological, geographic, behavioural and environmental analyses.

Alexandra Boccarossa / Horace Degnonvi / Télesphore Yao Brou / Marie Robbe-Saule / Lucille Esnault / Yan Boucaud / Matthieu Eveillard / Ronald Gnimavo / Saturnin Hounsou / Armel Djenontin / Christian Roch Johnson / Sébastien Fleuret / Estelle Marion

PLOS Global Public Health, Vol 2, Iss 1, p e

2022 Volume 0000095

Abstract: Buruli ulcer is a neglected tropical disease caused by M. ulcerans, an environmental mycobacterium. This cutaneous infectious disease affects populations with poor access to sanitation, safe water and healthcare living in rural areas of West and Central ... ...

Abstract	Buruli ulcer is a neglected tropical disease caused by M. ulcerans, an environmental mycobacterium. This cutaneous infectious disease affects populations with poor access to sanitation, safe water and healthcare living in rural areas of West and Central Africa. Stagnant open bodies of surface water and slow-running streams are the only risk factor identified in Africa, and there is no human-to-human transmission. Appropriate and effective prevention strategies are required for populations living in endemic areas. Based on a multidisciplinary approach in an area in which Buruli ulcer is endemic in South Benin, we investigated the link between all human-environment interactions relating to unprotected water and behaviors associated with Buruli ulcer risk likely to affect incidence rates. We characterised the sources of water as well as water bodies and streams used by communities, by conducting a prospective case-control study directly coupled with geographic field observations, spatial analysis, and the detection of M. ulcerans in the environment. A full list of the free surface waters used for domestic activities was generated for a set of 34 villages, and several types of human behaviour associated with a higher risk of transmission were identified: (i) prolonged walking in water to reach cultivated fields, (ii) collecting water, (iii) and swimming. Combining the results of the different analyses identified the risk factor most strongly associated with Buruli ulcer was the frequency of contact with unprotected and natural water, particularly in regularly flooded or irrigated lowlands. We confirm that the use of clean water from drilled wells confers protection against Buruli ulcer. These specific and refined results provide a broader scope for the design of an appropriate preventive strategy including certain practices or infrastructures observed during our field investigations. This strategy could be improved by the addition of knowledge about irrigation practices and agricultural work in low-lying areas.
Keywords	Public aspects of medicine ; RA1-1270
Subject code	910 ; 333
Language	English
Publishing date	2022-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Kinetic analysis of Cas12a and Cas13a RNA-Guided nucleases for development of improved CRISPR-Based diagnostics

Eric A. Nalefski / Nidhi Patel / Philip J.Y. Leung / Zeba Islam / Remy M. Kooistra / Ishira Parikh / Estelle Marion / Gavin J. Knott / Jennifer A. Doudna / Anne-Laure M. Le Ny / Damian Madan

iScience, Vol 24, Iss 9, Pp 102996- (2021)

2021

Abstract: Summary: Bacterial CRISPR systems provide acquired immunity against invading nucleic acids by activating RNA-programmable RNases and DNases. Cas13a and Cas12a enzymes bound to CRISPR RNA (crRNA) recognize specific nucleic acid targets, initiating ... ...

Abstract	Summary: Bacterial CRISPR systems provide acquired immunity against invading nucleic acids by activating RNA-programmable RNases and DNases. Cas13a and Cas12a enzymes bound to CRISPR RNA (crRNA) recognize specific nucleic acid targets, initiating cleavage of the targets as well as non-target (trans) nucleic acids. Here, we examine the kinetics of single-turnover target and multi-turnover trans-nuclease activities of both enzymes. High-turnover, non-specific Cas13a trans-RNase activity is coupled to rapid binding of target RNA. By contrast, low-turnover Cas12a trans-nuclease activity is coupled to relatively slow cleavage of target DNA, selective for DNA over RNA, indifferent to base identity, and preferential for single-stranded substrates. Combining multiple crRNA increases detection sensitivity of targets, an approach we use to quantify pathogen DNA in samples from patients suspected of Buruli ulcer disease. Results reveal that these enzymes are kinetically adapted to play distinct roles in bacterial adaptive immunity and show how kinetic analysis can be applied to CRISPR-based diagnostics.
Keywords	Chemical reaction kinetics ; Biochemistry ; Molecular biology ; Science ; Q
Subject code	572
Language	English
Publishing date	2021-09-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Molecular and epidemiological characterization of recurrent Mycobacterium ulcerans infections in Benin.

Ronald Gnimavo / Alban Besnard / Horace Degnonvi / Juliana Pipoli Da Fonseca / Marie Kempf / Christian Roch Johnson / Alexandra Boccarossa / Yao Télesphore Brou / Laurent Marsollier / Estelle Marion

PLoS Neglected Tropical Diseases, Vol 15, Iss 12, p e

2021 Volume 0010053

Abstract: 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 ...

Abstract	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.
Keywords	Arctic medicine. Tropical medicine ; RC955-962 ; Public aspects of medicine ; RA1-1270
Subject code	610
Language	English
Publishing date	2021-12-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Importance of consultations using mobile teams in the screening and treatment of neglected tropical skin diseases in Benin.

PLoS Neglected Tropical Diseases, Vol 17, Iss 5, p e

2023 Volume 0011314

Abstract: Context Since 2013, the World Health Organization has recommended integrated control strategies for neglected tropical diseases (NTDs) with skin manifestations. We evaluated the implementation of an integrated approach to the early detection and rapid ... ...

Abstract	Context Since 2013, the World Health Organization has recommended integrated control strategies for neglected tropical diseases (NTDs) with skin manifestations. We evaluated the implementation of an integrated approach to the early detection and rapid treatment of skin NTDs based on mobile clinics in the Ouémé and Plateau areas of Benin. Methods This descriptive cross-sectional study was performed in Ouémé and Plateau in Benin from 2018 to 2020. Consultations using mobile teams were performed at various sites selected by reasoned choice based on the epidemiological data of the National Program for the Control of Leprosy and Buruli Ulcer. All individuals presenting with a dermatological lesion who voluntarily approached the multidisciplinary management team on the day of consultation were included. The information collected was kept strictly anonymous and was entered into an Excel 2013 spreadsheet and analyzed with Stata 11 software. Results In total, 5,267 patients with various skin conditions consulted the medical team. The median age of these patients was 14 years (IQR: 7-34 years). We saw 646 (12.3%) patients presenting NTDs with skin manifestations, principally scabies, in 88.4% (571/646), followed by 37 cases of Buruli ulcer (5.8%), 22 cases of leprosy (3.4%), 15 cases of lymphatic filariasis (2.3%) and one case of mycetoma (0.2%). We detected no cases of yaws. Conclusion This sustainable approach could help to decrease the burden of skin NTDs in resource-limited countries.
Keywords	Arctic medicine. Tropical medicine ; RC955-962 ; Public aspects of medicine ; RA1-1270
Subject code	616
Language	English
Publishing date	2023-05-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Genome-wide association study of Buruli ulcer in rural Benin highlights role of two LncRNAs and the autophagy pathway

Jeremy Manry / Quentin B. Vincent / Christian Johnson / Maya Chrabieh / Lazaro Lorenzo / Ioannis Theodorou / Marie-Françoise Ardant / Estelle Marion / Annick Chauty / Laurent Marsollier / Laurent Abel / Alexandre Alcaïs

Communications Biology, Vol 3, Iss 1, Pp 1-

2020 Volume 10

Abstract: Jeremy Manry, Quentin Vincent et al. report a genome-wide association study for susceptibility to Buruli ulcer in a rural population from the West African country of Benin. They identify two independently associated variants within LncRNA genes and ... ...

Abstract	Jeremy Manry, Quentin Vincent et al. report a genome-wide association study for susceptibility to Buruli ulcer in a rural population from the West African country of Benin. They identify two independently associated variants within LncRNA genes and confirm the protective effect of a missense variant in the bacterial autophagy gene ATG16L1.
Keywords	Biology (General) ; QH301-705.5
Language	English
Publishing date	2020-04-01T00:00:00Z
Publisher	Nature Publishing Group
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Stable and Local Reservoirs of Mycobacterium ulcerans Inferred from the Nonrandom Distribution of Bacterial Genotypes, Benin

Clément Coudereau / Alban Besnard / Marie Robbe-Saule / Céline Bris / Marie Kempf / Roch Christian Johnson / Télésphore Yao Brou / Ronald Gnimavo / Sara Eyangoh / Fida Khater / Estelle Marion

Emerging Infectious Diseases, Vol 26, Iss 3, Pp 491-

2020 Volume 503

Abstract: Mycobacterium ulcerans is the causative agent of Buruli ulcer, a neglected tropical disease found in rural areas of West and Central Africa. Despite the ongoing efforts to tackle Buruli ulcer epidemics, the environmental reservoir of its pathogen remains ...

Abstract	Mycobacterium ulcerans is the causative agent of Buruli ulcer, a neglected tropical disease found in rural areas of West and Central Africa. Despite the ongoing efforts to tackle Buruli ulcer epidemics, the environmental reservoir of its pathogen remains elusive, underscoring the need for new approaches to improving disease prevention and management. In our study, we implemented a local-scale spatial clustering model and deciphered the genetic diversity of the bacteria in a small area of Benin where Buruli ulcer is endemic. Using 179 strain samples from West Africa, we conducted a phylogeographic analysis combining whole-genome sequencing with spatial scan statistics. The 8 distinct genotypes we identified were by no means randomly spread over the studied area. Instead, they were divided into 3 different geographic clusters, associated with landscape characteristics. Our results highlight the ability of M. ulcerans to evolve independently and differentially depending on location in a specific ecologic reservoir.
Keywords	Mycobacterium ulcerans ; Buruli ulcer ; genetic diversity ; mutational profiling ; genomic analysis ; geospatial model ; Medicine ; R ; Infectious and parasitic diseases ; RC109-216
Language	English
Publishing date	2020-03-01T00:00:00Z
Publisher	Centers for Disease Control and Prevention
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: High antibody titres induced by protein subunit vaccines using Mycobacterium ulcerans antigens Hsp18 and MUL_3720 with a TLR-2 agonist fail to protect against Buruli ulcer in mice

Kirstie M. Mangas / Nicholas J. Tobias / Estelle Marion / Jérémie Babonneau / Laurent Marsollier / Jessica L. Porter / Sacha J. Pidot / Chinn Yi Wong / David C. Jackson / Brendon Y. Chua / Timothy P. Stinear

PeerJ, Vol 8, p e

2020 Volume 9659

Abstract: Background Mycobacterium ulcerans is the causative agent of a debilitating skin and soft tissue infection known as Buruli ulcer (BU). There is no vaccine against BU. The purpose of this study was to investigate the vaccine potential of two previously ... ...

Abstract	Background Mycobacterium ulcerans is the causative agent of a debilitating skin and soft tissue infection known as Buruli ulcer (BU). There is no vaccine against BU. The purpose of this study was to investigate the vaccine potential of two previously described immunogenic M. ulcerans proteins, MUL_3720 and Hsp18, using a mouse tail infection model of BU. Methods Recombinant versions of the two proteins were each electrostatically coupled with a previously described lipopeptide adjuvant. Seven C57BL/6 and seven BALB/c mice were vaccinated and boosted with each of the formulations. Vaccinated mice were then challenged with M. ulcerans via subcutaneous tail inoculation. Vaccine performance was assessed by time-to-ulceration compared to unvaccinated mice. Results The MUL_3720 and Hsp18 vaccines induced high titres of antigen-specific antibodies that were predominately subtype IgG1. However, all mice developed ulcers by day-40 post-M. ulcerans challenge. No significant difference was observed in the time-to-onset of ulceration between the experimental vaccine groups and unvaccinated animals. Conclusions These data align with previous vaccine experiments using Hsp18 and MUL_3720 that indicated these proteins may not be appropriate vaccine antigens. This work highlights the need to explore alternative vaccine targets and different approaches to understand the role antibodies might play in controlling BU.
Keywords	Mycobacterium ulcerans ; Buruli ulcer ; Vaccination ; Mycobacterium ; Subunit vaccine ; ELISA ; Medicine ; R ; Biology (General) ; QH301-705.5
Subject code	630
Language	English
Publishing date	2020-08-01T00:00:00Z
Publisher	PeerJ Inc.
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: A combined effort of 11 laboratories in the WHO African region to improve quality of Buruli ulcer PCR diagnosis

Estelle Marion / Numfor Hycenth / Sundeep Chaitanya Vedithi / Marie Robbe-Saule / Valérie Donkeng / Line-Marlène Ganlonon / Affolabi Dissou / Solange Kakou Ngazoa / Marie-Jose Kabedi / Arsène Mabika Mabika / Richard Phillips / Michael Frimpong / Dorothy Yeboah-Manu / Vera Yatta Walker / Olaoluwa Akinwale / Maman Issaka / Gisela Bretzel / Kingsley Asiedu / Sara Eyangoh

PLoS Neglected Tropical Diseases, Vol 16, Iss 11, p e

The "BU-LABNET".

2022 Volume 0010908

Abstract: Buruli ulcer is one of the 20 neglected tropical diseases in the world. This necrotizing hypodermitis is a chronic debilitating disease caused by an environmental Mycobacterium ulcerans. At least 33 countries with tropical, subtropical and temperate ... ...

Abstract	Buruli ulcer is one of the 20 neglected tropical diseases in the world. This necrotizing hypodermitis is a chronic debilitating disease caused by an environmental Mycobacterium ulcerans. At least 33 countries with tropical, subtropical and temperate climates have reported Buruli ulcer in African countries, South America and Western Pacific regions. Majority of cases are spread across West and Central Africa. The mode of transmission is unclear, hindering the implementation of adequate prevention for the population. Currently, early diagnosis and treatment are crucial to minimizing morbidity, costs and preventing long-term disability. Biological confirmation of clinical diagnosis of Buruli ulcer is essential before starting chemotherapy. Indeed, differential diagnosis are numerous and Buruli ulcer has varying clinical presentations. Up to now, the gold standard biological confirmation is the quantitative PCR, targeting the insertion sequence IS2404 of M. ulcerans performed on cutaneous samples. Due to the low PCR confirmation rate in endemic African countries (under 30% in 2018) for numerous identified reasons within this article, 11 laboratories decided to combine their efforts to create the network "BU-LABNET" in 2019. The first step of the network was to harmonize the procedures and ship specific reagents to each laboratory. With this system in place, implementation of these procedures for testing and follow-up was easy and the laboratories were able to carry out their first quality control with a very high success rate. It is now time to integrate other neglected tropical diseases to this platform, such as yaws or leprosy.
Keywords	Arctic medicine. Tropical medicine ; RC955-962 ; Public aspects of medicine ; RA1-1270
Subject code	610
Language	English
Publishing date	2022-11-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Buruli ulcer in South Western Nigeria

Estelle Marion / Kevin Carolan / Ambroise Adeye / Marie Kempf / Annick Chauty / Laurent Marsollier

PLoS Neglected Tropical Diseases, Vol 9, Iss 1, p e

a retrospective cohort study of patients treated in Benin.

2015 Volume 3443

Abstract: Nigeria is known to be endemic to Buruli ulcer, but epidemiological data are remarkably rare. Here, we present a large cohort of 127 PCR-confirmed M. ulcerans infection patients coming from Nigeria and treated in a neighbouring country, Benin. Severe ... ...

Abstract	Nigeria is known to be endemic to Buruli ulcer, but epidemiological data are remarkably rare. Here, we present a large cohort of 127 PCR-confirmed M. ulcerans infection patients coming from Nigeria and treated in a neighbouring country, Benin. Severe lesions and delay of consultation are factors that should encourage establishment of a treatment centre in South Western Nigeria.
Keywords	Arctic medicine. Tropical medicine ; RC955-962 ; Public aspects of medicine ; RA1-1270
Language	English
Publishing date	2015-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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