The severe and often lethal disease Anthrax has been known since antiquity, and is caused by the spore-forming, gram-positive bacterium, Bacillus anthracis (B. a). After spores enter through an open wound, the host develops cutaneous Anthrax, which is identified by the development of typical black colored lesions, eschars. The name Anthrax itself derives from the Greek word for coal. Interestingly, the cause of the black eschars is not understood nor has their role in anthrax pathogenesis or host defense been adequately investigated. We set out to understand the cellular mechanism responsible for the formation of these black lesions, as well as understanding their role in disease progression. Bacillus anthracis secretes two toxic factors, Edema Factor (EF) and Lethal factor (LF), both paralyze the immune response in the early phase of infection and promote alarming symptoms in the later stages of the disease. Edema Factor is a potent Adenylate Cyclase, that leads to an uncontrolled rise in cAMP concentration, and is responsible for edema; whereas lethal toxin is a zinc metalloprotease that cleaves MAPKK ultimately inhibiting cell growth and division. From experiments in Drosophila melanogaster transgenically expressing anthrax toxins, we find that cAMP signaling promotes pigmentation through a defined pathway mediated by Protein Kinase A (PKA). PKA is known to cause specific phosphorylation and activation of Tyrosine Hydroxylase (TH) the rate-limiting enzyme required for melanin synthesis. Examination of Tyrosine Hydroxylase in Drosophila melanogaster in response to EF expression shows a direct relationship with pigmentation and revealed novel phenotypes of Anthrax modeled in this insect system. We propose that a similar mechanism is at play in human cells, and that EF and LF may act similarly in melanocytes, potentially leading to uncontrolled melanogenesis in anthrax-infected skin tissues. Ultimately, this leads to the question as to whether these black cutaneous lesions are a product of host defense aimed at controlling the spread of the pathogen, or whether they are a part of Bacillus anthracis virulence strategy
