Mycobacterium Ulcerans

Mycobacterium ulcerans - Buruli ulcer

buruli mapWithin the past decade, the incidence of Buruli ulcer has dramatically increased in several countries in sub-Saharan Africa, Australia, Asia, Mexico, and Peru, leading the WHO to declare this disease a global health threat in 2004. Despite being the third most common mycobacterial disease in immunocompetent humans after tuberculosis and leprosy, Buruli ulcer is considered a “neglected tropical disease” by the WHO and does not garner the attention given to other infectious diseases. The WHO estimates that the incidence of Buruli ulcer will surpass that of leprosy and could become more problematic than tuberculosis in some African regions.

 



Mycobacterium ulcerans

Mycobacterium ulcerans, the microorganism that causes Buruli ulcer, is a slow-growing environmental mycobacterium of which the natural reservoir is unknown. Human transmission is believed to occur via skin transmission by direct inoculation or an insect vector. Most individuals infected with M. ulcerans initially develop a small, painless, pre-ulcerative skin nodule with larger areas of indurated skin and edema. As the disease progresses over one to two months, the infected skin begins to ulcerate with characteristic necrosis of the subcutaneous fatty tissues, deeply undermined edges, and vascular blockage. These necrotic ulcers can lead to very extensive skin loss, damage to nerves, blood vessels, and appendages, and deformity and disability, particularly in children.

Currently, no vaccine is available for the prevention of Buruli ulcer.  Although antibiotic treatment has been shown to be effective in vitro and in animal models, success in the clinical environment has produced variable results, especially in the case of advanced ulcerative disease.  Accordingly, surgical excision, combined with antibiotic therapy, prevails as an accepted remedy for these difficult-to-treat infections.

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Treatment of Buruli ulcer with clay minerals

buruli clay mineral in flaskDocumented use of two clay minerals as a therapeutic treatment for the necrotizing Mycobacterium ulcerans skin infection, Buruli ulcer, suggests that specific natural mineral products have significant beneficial effects on wound healing. In 2001, a French humanitarian working in the Ivory Coast of Africa began treating children with Buruli ulcer with natural clay minerals. Within days of initiating treatment with clay poultices, the therapeutic properties of the clay minerals were demonstrated, with the initiation of rapid, non-surgical debridement of the destroyed tissue. Extended treatment with the clay minerals resulted in continued debridement of the ulcer, tissue regeneration, and wound healing. After several months of daily clay applications, the Buruli ulcer wounds healed with soft, supple scarring and return of normal motor function.

     


Projects

Characterization and mechanism of action of antibacterial clay minerals and synthetic derivatives; Mycobacterium ulcerans - Buruli ulcer

In 2001, a French humanitarian described the use of clay minerals as a therapeutic treatment of Buruli ulcer. Recently, various mineral products marketed for their health benefits have been investigated for their potential antimicrobial properties. However, only a small number of clay products have been shown to be antibacterial and the mechanism of antibacterial activity has been elucidated for very few of these products. Our lab investigates the mechanism(s) by which specific clay minerals can kill bacteria and the feasibility of using natural mineral products as alternative therapies for topical infections.

 


 

Assess the broad-spectrum antibacterial effects of specific clay minerals and mineral derivatives

 

We subjected the two iron-rich clay minerals, which were used to treat Buruli ulcer patients, to broth culture susceptibility testing of antibiotic-susceptible and antibiotic-resistant pathogenic bacteria to assess the feasibility of using clay minerals as therapeutic agents. One specific clay mineral sample, Ag02, demonstrated bactericidal activity against beta-lactamase (ESBL) E. coliS. enterica serovar Typhimurium, Pseudomonas aeruginosa, and Mycobacterium marinum and a combined bacteriostatic/bactericidal effect against Staphylococcus aureus, penicillin-resistant S. aureus (PRSA), and methicillin-resistant S. aureus (MRSA), while another mineral with similar structure and bulk crystal chemistry, CsAr02, had no effect on or enhanced bacterial growth (Haydel et al. 2008).

 

We have screened over 50 clay mineral mixtures sold as health and cosmetic products and identified two additional clay mineral mixtures (arbitrarily named BY07 and CB07) with antibacterial activity, indicating that antibacterial minerals are diverse and that the associated health benefits may be related to bactericidal activity (Cunningham et al. 2010).

Further investigations revealed that filtered aqueous suspensions (leachates), devoid of all physical minerals, exhibit antimicrobial activity as well, indicating that the bactericidal activity of the clay mineral mixtures was due to chemical as opposed to physical properties of the clay (Cunningham et al. 2010, Otto et al. 2011).

 

   
 

 


 

Determine the mechanism(s) of action of antibacterial clay minerals

We are investigating the possible mechanism by which the clays kill bacteria by assessing potential physical damage to the bacterial cells and cellular physiological damage caused by the chemical properties of the clay minerals.

Scanning electron microscopy (SEM) and transmission electron microscopy (TEM) imaging of E. coli and MRSA revealed intact cells following exposure to antibacterial mineral leachates (Otto et al. 2011). Further investigations revealed that the clay mineral leachate antibacterial mechanism of action differs for Gram-positive and Gram-negative organisms. While overal structural integrity is retained, compromised membrane integrity accounts for bactericidal activity in Gram-positive, but not in Gram-negative bacterial cells (Otto et al. 2011).

Additional experiments to determine the mechanism of action and to identify the specific cellular targets of antibacterial activity are currently underway.

 


Evaluate the effectiveness of antibacterial clay poultices and nanomineral-derived solutions to promote wound healing

The long-term goal of this research is to validate mineral applications for the treatment of Buruli ulcer patients and to develop a new broad-spectrum antibacterial product for cutaneous infections that are difficult to treat due to ineffecient antibiotics, innate or acquired resistance, or the requirement of an extended treatment regimen. Our objective is to evaluate the in vivo efficacy of clay minerals and mineral solutions in the experimental treatment of topical infections.