Bactericidal Activity of Rifampin-Amikacin against
            <i>Mycobacterium ulcerans</i>
            in Mice

Dega, Hervé; Bentoucha, Abdelhalim; Robert, Jérôme; Jarlier, Vincent; Grosset, J

doi:10.1128/aac.46.10.3193-3196.2002

Cited by 75 publications

(100 citation statements)

References 10 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…19 In conclusion, our observations, combined with previous reports, 16 suggest that soil contaminated with M. ulcerans could serve as a transient infectious source for BU. The observations reported here might prompt field observers to assess whether the soil in regions affected by BU is naturally contaminated.…”

Section: Table 1 Summary Of Experimental Procedures and Final Resultssupporting

confidence: 59%

“…16 Mycobacterium ulcerans was not cultured from the lesions but its DNA was reliably detected in three of 10 inoculated footpads by RT-PCR.…”

Section: Table 1 Summary Of Experimental Procedures and Final Resultsmentioning

confidence: 99%

“…15 A previously reported M. ulcerans mouse model was used with modifications. 16 The animal model protocol no. 02552.02 was reviewed and approved by the "Comité d'Ethique de Marseille C2EA-14" and "Comité National de Reflexion éthique sur l'expérimentation animale" on November 17, 2014.…”

mentioning

confidence: 99%

See 2 more Smart Citations

Experimental Survival of Mycobacterium ulcerans in Watery Soil, a Potential Source of Buruli Ulcer

Tian¹,

Lépidi²,

Nappez³

et al. 2016

The American Society of Tropical Medicine and Hygiene

View full text Add to dashboard Cite

Abstract. The reservoir of Mycobacterium ulcerans causing Buruli ulcer (BU) remains unknown. Here, sterilized watery soil was mixed with 2 × 10 6 colony-forming units (CFU)/g of M. ulcerans Agy99 or M. ulcerans ATCC 33728 and incubated in a microaerophilic atmosphere in the presence of negative controls. Both M. ulcerans strains survived in soil for 4 months with a final inoculum of 300-440 CFU/g. Further, three groups of five mice with and without footpad scarification were exposed to control soil or M. ulcerans-inoculated soil. Although no specific clinical and histopathological lesions were observed in control animals, red spots observed on 8/20 scarified feet in 8/10 challenged mice yielded inflammatory infiltrates and positive real-time polymerase chain reaction detection of M. ulcerans DNA in five mice. BU can be acquired as an inoculation infection with watery soil as a transient source of infection. These experimental observations warrant additional field observations. Moreover, the only environmental M. ulcerans isolate was recovered from a water strider in Benin. 7 These observations suggest a link between BU and stagnant and slow-flowing aquatic environments in West Africa. However, freshwater itself may not be the ultimate source of M. ulcerans. In particular, fishermen who are presumably in frequent contact with water have a lower prevalence of BU than other groups in endemic regions in Africa. 8,9 In addition, the M. ulcerans inoculum has been estimated to be 100-1,000 mycobacteria/mL in water, based on real-time polymerase chain reaction (RT-PCR) targeting IS2404.3 This estimated inoculum level is three to four times lower than the levels reported for major waterborne human pathogens such as Vibrio. 10We have recently shown that Mycobacterium tuberculosis, a Mycobacterium that is phylogenetically closely related to M. ulcerans, retains its infectivity after an extended stay in soil. 11 We therefore hypothesized that watery soil could be a source of M. ulcerans.To test the hypothesis, M. ulcerans ATCC 19423 TMT (strain Agy99) and M. ulcerans ATCC 33728 (both obtained from the American Type Culture Collection, Masassas, VA) were cultured in an incubator at 32°C on Middlebrook 7H10 Agar (Becton Dickinson, Le Pont de Claix, France), supplemented with OADC (oleic acid, bovine albumin, dextrose, and catalase) (Becton Dickinson). Natural soil was steam sterilized at 134°C for 15 minutes, and the sterility was then assessed by inoculating 2 g of steam-sterilized soil onto Middlebrook 7H10 Agar incubated at 32°C for 4 weeks. A 20-g sample of sterilized soil was inoculated and mixed with 2 × 10 6 colonyforming units (CFU)/g of each of the two M. ulcerans isolates, placed into 25-cm 2 cell culture flasks (Corning, Corning, NY) and thoroughly mixed. Three flasks were prepared for each M. ulcerans strain. The flasks were placed inside a transparent sterile plastic container where they were exposed to a microaerophilic atmosphere created using a CampyGen atmosphere generation system (Oxoid Ltd., Basingstoke, Un...

show abstract

Section: Table 1 Summary Of Experimental Procedures and Final Resultssupporting

confidence: 59%

“…16 Mycobacterium ulcerans was not cultured from the lesions but its DNA was reliably detected in three of 10 inoculated footpads by RT-PCR.…”

Section: Table 1 Summary Of Experimental Procedures and Final Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Experimental Survival of Mycobacterium ulcerans in Watery Soil, a Potential Source of Buruli Ulcer

Tian¹,

Lépidi²,

Nappez³

et al. 2016

The American Society of Tropical Medicine and Hygiene

View full text Add to dashboard Cite

show abstract

“…The initial onset of redness, observed between days 25 and 28 after inoculation, is followed, 10 d later, by an edema with signs of ulceration. As expected (13,14), 45 d after inoculation, in BALB/c and C57BL/6 mice, ulceration evolve to progressive and irreversible necrosis and, consequently, animals were sacrificed at day 75 (Fig. 1A).…”

Section: Resultsmentioning

confidence: 92%

“…Usually, all preclinical studies of M. ulcerans infection are performed in a mouse model, using either BALB/c or C57BL/6 mouse strains, and they study host colonization or evaluate efficacy of treatments or vaccines (7,(10)(11)(12)(13)(14). As a matter of fact, in both strains, s.c. inoculation with M. ulcerans invariably leads to ulceration after several weeks, with lesions evolving toward tissue necrosis and death of the animals.…”

mentioning

confidence: 99%

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

View full text Add to dashboard Cite

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.

show abstract

Buruli Ulcer

Scherr

Pluschke

2019

Neglected Tropical Diseases

View full text Add to dashboard Cite

Bactericidal Activity of Rifampin-Amikacin against Mycobacterium ulcerans in Mice

Cited by 75 publications

References 10 publications

Experimental Survival of Mycobacterium ulcerans in Watery Soil, a Potential Source of Buruli Ulcer

Experimental Survival of Mycobacterium ulcerans in Watery Soil, a Potential Source of Buruli Ulcer

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

Buruli Ulcer

Contact Info

Product

Resources

About