Mycobacterium ulcerans mycolactone interferes with adhesion, migration and proliferation of primary human keratinocytes and HaCaT cell line

The pathogenicity of Mycobacterium ulcerans( Buruli ulcer) is closely associated with the secretion of exotoxin mycolactone. The cytotoxicity of mycolactonehas been linked to its apoptogenic activity. We explored if low mycolactoneconcentrations, which are not able to induce apoptosis, can influence other essential activities on two primary human keratinocytepopulations, keratinocytestem cells (KSC) and transit amplifying cells (TAC), and on a human keratinocyteline, HaCaT. We demonstrated that 0.01 and 0.1 ng/ml mycolactoneA/B are not able to induce apoptosis in primary human keratinocytes, but interfere with KSC wound repair. Moreover, the same toxin concentrations reduce cell proliferation of KSC and TAC and their ability to adhere to type IV collagen. HaCaTcells are more resistant to the toxin; nevertheless, they show a delayed woud repair when treated with 1 and 10 ng/ml mycolactoneA/B. Moreover, these sub-apoptotic concentrations affect their ability to proliferate and adhere to collagen IV. Wound healing is a complex mechanism, which occurs “in vivo” as the outcome of many co-ordinated events. Sub-apoptotic mycolactoneconcentrations can affect essential mechanisms, which are required to achieve wound repair, such as adhesion, migration and proliferation of human keratinocytes.