Sequencing L. donovani mutant parasites PTP1, PTP2, the double PTP knockout and DUF21
Leishmania donovani causes the neglected tropical disease known as visceral leishmaniasis. L. donovani contains two PTP proteins (protein tyrosine phosphatase 1 &amp; 2) and a DUF21 protein (domain of unknown function 21) which are respectively homologous to mammalian PRL (phosphatases of regenerating liver) and mammalian CNNM (cyclin M family). In mammals these proteins can bind and regulate intracellular magnesium. Herein, we revealed that L. donovani PTP2 and DUF21 can also form a specific protein complex. We next generated mutant parasites: LdPTP1, LdPTP2, a double knockout termed LdPTP1/2 and LdDUF21. The LdPTP1/2 mutant could not survive in low magnesium media and had a reduced survival level in infected macrophages. Whereas LdDUF21 is sensitive to high levels of magnesium, has an increased level of intracellular magnesium and an increased survival in macrophages. Together, these observations provide evidence that in L. donovani PTP and DUF21 can complex and respond to environmental magnesium.