Inactivation of the cytosolic and mitochondrial serine hydroxymethyl transferase genes in Leishmania major

• Leishmania has a cytosolic (cSHMT) and a mitochondrial (mSHMT) serine hydroxymethyl transferase.
• Inactivation of cSHMT or mSHMT or of both genes is possible in Leishmania.
• Leishmania cells without SHMT grow well if supplemented with serine.
• Serine is important for the growth of Leishmania.

Leishmania has two serine hydroxylmethyl transferase (SHMT) genes, one coding for a cytosolic and the other for a mitochondrial enzyme. Trypanosoma cruzi has only the gene coding for the cytosolic enzyme and Trypanosoma brucei has no SHMT. We tested whether these genes were dispensable for growth in Leishmania major. By gene inactivation we succeeded in generating three cells lines one without the cytosolic cSHMT, one without the mitochondrial mSHMT, and finally one L. major line without any SHMT. SHMT is thus dispensable for growth of Leishmania in rich medium. The ability of the various shmt null mutants to grow in defined medium was tested and the growth of the shmt null mutant was dependent on the presence of serine. Overall this work has shown that SHMT is dispensable for Leishmania growth but it may be necessary when growing in environments poor in serine.

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