NEW YORK (Reuters Health) - The virulence of Mycobacterium ulcerans infection, the causative agent of Buruli ulcer, appears to be mediated by mycolactone, an unusual plasmid-encoded toxin, according to a multinational team. This emerging human pathogen is harbored by aquatic insects.
Buruli ulcers, caused by extracellular infection with the organism, are rife in Central and West Africa and can involve more than 15% of a person’s skin surface, Dr. Stewart T. Cole, a microbiologist at Institut Pasteur in Paris, and his associates point out.
Furthermore, “there is a remarkable absence of an acute inflammatory response to the bacteria, and the lesions are often painless,” the authors add in their report in the Proceedings of the National Academy of Sciences published online January 19.
Their research revealed the presence of a seemingly simple plasmid with a cluster of genes encoding giant polyketide synthases (PKS) and polyketide-modifying enzymes that produce the macrolide toxin mycolactone. The PKS proteins are “of unprecedented size.” The genome is composed of 16 extension modules of high sequence similarity.
According to Dr. Cole’s team, the high level of DNA sequence homology suggests that the toxin-encoding system has evolved quite recently, and is characterized by a high level of genetic instability.
“High mutability may explain the sudden appearance of Buruli ulcer epidemics as some strains produce mycolactones that confer a fitness advantage for an environmental niche such as the salivary glands of particular aquatic insects,” Dr. Cole and associates conclude. The genetic instability may also be related to increased virulence or transmissibility.
They hope that further investigation of the plasmid-toxin apparatus will lead to new ways to prevent and combat M. ulcerans infections.
Source: Proc Natl Acad Sci USA 2004.www.pnas.org/cgi/doi/10.1073/pnas.0305877101 [ Google search on this article ]
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