Mycobacterium ulcerans Agy99

In 1948 the etiologic agent of the Bairnsdale ulcer in humans was discovered by a team of Australian researchers and was named Mycobacterium ulcerans. During the 1960s many cases were reported from the Buruli County in Uganda and the disease became generally known as Buruli ulcer. The Buruli ulcer is a devastating necrotic disease of subcutaneous tissue and a single Buruli ulcer can cover more than 15% of a person's skin surface and contains huge numbers of extracellular bacteria. Despite their abundance and extensive tissue damage, there is no acute inflammatory response to the bacteria and the lesions are often painless. This pathology is attributed to mycolactone, a macrolide toxin. Impoverished rural communities of West and Central Africa are worst affected although the disease occurs in other parts of the world. Since 1989, the prevalence of Buruli ulcer has increased and now exceeds that of leprosy and, in some instances, tuberculosis. Outbreaks are sporadic and unpredictable. Although the epidemiology of Buruli ulcer is poorly understood, proximity to stagnant or slow-flowing watercourses is a recognized risk factor. M. ulcerans is associated with algae, therefore, snails and organisms that feed on algae could be passive hosts. It has been shown that M. ulcerans is able to multiply in the salivary glands of Naucoris cimicoides, a carnivorous water bug. Humans could become infected through contact with contaminated Naucorides. Mycobacterium ulcerans (strain Agy99) was isolated from an ulcerative lesion on the right elbow of a female patient from the Ga district of Ghana in 1999. Its genome is made up of a 5.6 Mb chromosome and a 174,155-bp plasmid. The chromosome contains 4160 CDS and 771 pseudogenes, it harbors two prophages, phiMU01 and phiMU02, 302 insertion sequence elements and multiple DNA deletions and rearrangements. This indicates that M. ulcerans has recently evolved via lateral gene transfer and reductive evolution from the generalist, more rapid-growing environmental Mycobacterium marinum to become a niche-adapted specialist. The virulence plasmid pMUM001 encodes 81 CDS. Six CDS code for proteins involved in mycolactone synthesis, among which, mlsA1 and mlsA2, two giant polyketide synthases (PKS) responsible for the synthesis of the mycolactone core, and mlsB which is responsible for the synthesis of the mycolactone side chain. (EBI Integr8)