Use of the Immunodominant 18-Kilodalton Small Heat Shock Protein as a Serological Marker for Exposure to
            <i>Mycobacterium ulcerans</i>

Díaz, David; Döbeli, Heinz; Yeboah-Manu, Dorothy; Mensah-Quainoo, Ernestina; Friedlein, Arno; Soder, Nicole; Rondini, Simona; Bodmer, Thomas; Pluschke, Gerd

doi:10.1128/cvi.00254-06

Cited by 57 publications

(85 citation statements)

References 38 publications

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“…Surprisingly, histological approaches showed that the bacilli present in healed tissues are not surrounded by a granuloma-like structure, unlike in the context of latent tuberculosis (42,43). Moreover, this model supports the concept that interindividual variability in the host response to infection by M. ulcerans could be accounted for, at least in part, by host genetic factors (44)(45)(46).…”

Section: Major Data Model Descriptionsupporting

confidence: 65%

FVB/N Mice Spontaneously Heal Ulcerative Lesions Induced by Mycobacterium ulcerans and Switch M. ulcerans into a Low Mycolactone Producer

Marion

Jarry

Cano

et al. 2016

The Journal of Immunology

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Buruli ulcer, a debilitating disease, is caused by Mycobacterium ulcerans. The incidence of this neglected tropical disease is steadily increasing. As a rule, without treatment, skin ulcers occur and a lengthy healing process may be observed associated with severe functional disabilities. Mouse models are already available to study establishment of lesions or evaluation of therapy but a lack of a suitable animal model, mimicking all clinical stages, in particular the healing process, remains an obstacle to understand the pathophysiology of M. ulcerans infection. M. ulcerans was s.c. inoculated in three consanguine mouse strains, that is, BALB/c and C57BL/6, classically used to study mycobacterial infection, and FVB/N. Strikingly, FVB/N mice, although as sensitive as all other mouse strains with respect to M. ulcerans infection, presented a spontaneous healing after the ulcerative phase despite stable bacterial load, and mycolactone toxin was not detected in the healed tissues. The spontaneous healing process was accompanied by an activation of the innate immune system. The adaptive response initiated by FVB/N mice was not involved in the healing process and did not confer protection against M. ulcerans. Our work highlights the importance of innate immune responses to control M. ulcerans infection. This in vivo model of M. ulcerans infection now paves the way for new avenues of research toward the elucidation of critical stages of this disease, such as the characterization of the regulation of mycolactone production, a better understanding of the pathophysiology of M. ulcerans infection, and the development of new therapeutic strategies.

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Section: Major Data Model Descriptionsupporting

confidence: 65%

FVB/N Mice Spontaneously Heal Ulcerative Lesions Induced by Mycobacterium ulcerans and Switch M. ulcerans into a Low Mycolactone Producer

Marion

Jarry

Cano

et al. 2016

The Journal of Immunology

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“…The strains used for this investigation and their origins are as follows: M. ulcerans Agy99, Malaysia 1615, and Japan 753 (21); Ghana IFIK1066089, Ghana Nm50/ 04, Ghana Nm51/04, Ghana Nm53/04, Ghana Nm74/02, Ghana Nm97/02, Ghana Nm98/02, Ghana Nm103/02, and Mexico IFIK 973880 (this study); Ghana Nm18/ 02, Ghana Nm21/02, Ghana Nm31/04, Ghana Nm38/02, and Ghana Nm59/02 (10) (5). Mycobacteria were obtained from cultures as described earlier (19,31), resuspended in phosphate-buffered saline (PBS; pH 7.4), and heat inactivated at 95°C for 60 min.…”

Section: Methodsmentioning

confidence: 63%

Optimized Method for Preparation of DNA from Pathogenic and Environmental Mycobacteria

Käser

Ruf

Hauser

et al. 2009

Appl Environ Microbiol

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Genomic studies on pathogenic and environmental mycobacteria are of growing interest for understanding of their evolution, distribution, adaptation, and host-pathogen interaction. Since most mycobacteria are slow growers, material from in vitro cultures is usually scarce. The robust mycobacterial cell wall hinders both experimental cell lysis and efficient DNA extraction. Here, we compare elements of several DNA preparation protocols and describe a method that is economical and practical and reliably yields large amounts-usually 10-fold increased compared to earlier protocols-of highly pure genomic DNA for sophisticated downstream applications. This method was optimized for cultures of a variety of pathogenic and environmental mycobacterial species and proven to be suitable for direct mycobacterial DNA extraction from infected insect specimens.Mycobacterial diseases are a major health concern for humans (i.e., Mycobacterium tuberculosis, M. leprae, M. ulcerans, M. avium, and M. paratuberculosis) (4, 13, 18, 29, 30) (13,20). Efficient methods for DNA preparation are required both for the identification and genotyping of such pathogens and for population genomics, which is developing into an important tool to study bacterial evolution, virulence, and epidemiology.Extraction of mycobacterial genomic DNA is especially demanding since (i) many mycobacterial species are among the most extreme slow growers, accounting for small amounts of starting material, and (ii) a robust and waxy cell wall renders mycobacteria difficult to lyse. Published protocols for mycobacterial DNA preparations and commercially available extraction kits are mainly designed for the isolation of small amounts of genomic material suitable for conventional PCR application (2,7,9,11,14,15,23,24,27,28,33), such as for testing of potentially contaminated milk (6,8,17). However, such DNA quantities and qualities are usually not sufficient for more sophisticated molecular analyses.M. ulcerans, the causative agent of the devastating human skin disease Buruli ulcer, is one of the slowest growers among mycobacterial species, and the development of molecular tools is crucial for studying its transmission and microepidemiology. The objective of this study was to develop an optimized extraction protocol for DNA of both high quantity and quality from scarce material of in vitro-cultivated M. ulcerans disease isolates. We compared elements of several protocols and developed a DNA preparation method that is optimized in each individual step and thus ready to use for virtually all mycobacterial species to yield a maximum of pure genetic material. In addition, we applied the established method to cultures of a variety of pathogenic and environmental mycobacterial species and tested it by isolating DNA from insects experimentally infected with M. ulcerans. MATERIALS AND METHODSMycobacterial strains and preparation of mycobacterial cell suspensions. The strains used for this investigation and their origins are as follows: M. ulcerans Agy99, Malaysia 1615, and Japa...

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“…The observations that active BU occurs in a small proportion of exposed individuals (14,58) and when it develops frequently heals spontaneously (69) suggest the existence of protective immunity. Although the protective mechanisms remain largely unknown, several studies support that adaptive cell-mediated immunity (CMI) is relevant for the control of M. ulcerans (reviewed in reference 53).…”

mentioning

confidence: 99%

Mycobacterium ulcerans Triggers T-Cell Immunity followed by Local and Regional but Not Systemic Immunosuppression

et al. 2011

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Buruli ulcer is a neglected infectious disease caused byBuruli ulcer (BU) is an emerging neglected tropical disease caused by Mycobacterium ulcerans and is characterized by nonulcerative lesions that can evolve into severe ulcers (41,70).Infection by M. ulcerans poses a unique challenge for the host immune system due to the secretion of the highly cytotoxic lipidic exotoxin mycolactone (17). Mycolactone has been suggested to suppress the development of local and systemic immune responses by inhibiting cytokine production during active BU (19-21, 42, 72, 75) and compromising T-cell priming by suppressing dendritic cell function (11). However, there are no studies on the association of BU with opportunistic infections, suggesting that the immunosuppressive effects of mycolactone might not be systemic.The observations that active BU occurs in a small proportion of exposed individuals (14, 58) and when it develops frequently heals spontaneously (69) suggest the existence of protective immunity. Although the protective mechanisms remain largely unknown, several studies support that adaptive cell-mediated immunity (CMI) is relevant for the control of M. ulcerans (reviewed in reference 53). In fact, (i) M. ulcerans has an intramacrophage growth phase (66), (ii) resistance to BU is associated with the development of T helper (Th) 1 type responses and granulomata (10,20,21,23,42,48,63,70,72), (iii) the positivity of the delayed-type hypersensitivity (DTH) burulin test increases from early to advanced phases (15, 31), (iv) the histopathology of healing BU lesions in patients submitted to antibiotic treatment is consistent with CMI (49), (v) Mycobacterium bovis BCG vaccination induces transient protection in humans and in experimental infections (16,55,60,62,68), (vi) infection with HIV increases the risk of developing BU and more aggressive multifocal forms (27, 64), and (vii) the pattern of cytokine expression in BU lesions conforms with CMI and DTH (28,38,67).Therefore, to clarify whether the M. ulcerans infectious process interferes with the development of protective immunity and whether systemic immunosuppression is induced, we monitored the host immune response in the mouse model, not only in the primary site of infection but also in the draining lymph node (DLN), where the initiation of the adaptive immunity takes place. MATERIALS AND METHODSAnimals. Eight-week-old female wild-type, nude, and Rag2-deficient mice in a BALB/c background were obtained from Charles River (Barcelona, Spain). Rag-deficient BALB/c mice transgenic for the DO11.10 ␣/␤ T-cell receptor (TCR) were from Anne O'Garra (NIMR, London, United Kingdom). The studies involving animals were approved by the review committees of ICVS and the Portuguese Governmental Agency Direcção Geral de Veterinária.Experimental infections. The different M. ulcerans strains used in the present study were selected based on their virulence for mice (35,65) and on the type of mycolactone produced (26, 32, 59). M. ulcerans 5114 is a low-virulence Mexican

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Use of the Immunodominant 18-Kilodalton Small Heat Shock Protein as a Serological Marker for Exposure to Mycobacterium ulcerans

Cited by 57 publications

References 38 publications

FVB/N Mice Spontaneously Heal Ulcerative Lesions Induced by Mycobacterium ulcerans and Switch M. ulcerans into a Low Mycolactone Producer

FVB/N Mice Spontaneously Heal Ulcerative Lesions Induced by Mycobacterium ulcerans and Switch M. ulcerans into a Low Mycolactone Producer

Optimized Method for Preparation of DNA from Pathogenic and Environmental Mycobacteria

Mycobacterium ulcerans Triggers T-Cell Immunity followed by Local and Regional but Not Systemic Immunosuppression

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