Deletion of an ATP-binding cassette protein subfamily C transporter in Leishmania donovani results in increased virulence

Genome comparison of Leishmania species sequenced to date has identified several hundred differentially distributed genes which are present as functional genes in some species but as pseudogenes or absent in others. It is not clear whether these differentially distributed genes are important for disease, redundant or even harmful for a particular Leishmania species though a few of these genes have been implicated in Leishmania infection tissue tropism. The L. infantum LinJ.24.1510 gene is an ATP-binding cassette transporter protein subfamily C member which is present in L. donovani complex species and L. mexicana but absent in L. major and L. braziliensis and its substrate is unknown. Experimental deletion of this gene from L. donovani has resulted in an increase in growth as axenic amastigotes and increased virulence in infecting mice. To our knowledge, this is the first gene identified in Leishmania where its deletion results in hypervirulence.

Graphical abstractLd.24.1510 gene encodes a novel ATP-binding cassette protein which is differentially distributed in Leishmania species. Deletion of Ld.24.1510 gene in Leishmania donovani resulted in hypervirulence.Download high-res image (112KB)Download full-size imageHighlights► Ld.24.1510 gene is present in L. donovani complex species and L. mexicana. ► Ld.24.1510 gene is absent in L. major and L. braziliensis. ► Ld.24.1510 gene encodes an ATP-binding cassette protein subfamily C transporter. ► Ld.24.1510 null mutant grows better than wild type cell as axenic amastigote. ► Ld.24.1510 null mutant is more virulent than wild type cell in infecting mice.