Cystathionine γ-lyase, an Enzyme Related to the Reverse Transsulfuration Pathway, is Functional in Leishmania spp.

LUCILA GIORDANA; BRIAN SUÁREZ MANTILLA; MARIANELA SANTANA; ARIEL M. SILBER; CRISTINA NOWICKI

JOURNAL OF EUKARYOTIC MICROBIOLOGY

WILEY-BLACKWELL PUBLISHING, INC

Lugar: Londres; Año: 2014

1066-5234

Leishmania parasites seem capable of producing cysteine by de novo biosynthesis,similarly to bacteria, some pathogenic protists, and plants. In Leishmaniaspp., cysteine synthase (CS) and cystathionine b-synthase (CBS) areexpected to participate in this metabolic process. Moreover, the reverse transsulfurationpathway (RTP) is also predicted to be operative in this trypanosomatidbecause CBS also catalyzes the condensation of serine withhomocysteine, and a gene encoding a putative cystathionine c-lyase (CGL) ispresent in all the sequenced genomes. Our results show that indeed, Leishmaniamajor CGL is able to rescue the wild-type phenotype of a Saccharomycescerevisiae CGL-null mutant and is susceptible to inhibition by anirreversible CGL inhibitor, DL-propargylglycine (PAG). In Leishmania promastigotes,CGL and CS are cytosolic enzymes. The coexistence of de novo synthesiswith the RTP is extremely rare in most living organisms; however, despitethis potentially high redundancy in cysteine production, PAG arrests the proliferationof L. major promastigotes with an IC50 of approximately 65 lM. Thesefindings raise new questions regarding the biological role of CGL in thesepathogens and indicate the need for understanding the molecular mechanismof PAG action in vivo to identify the potential targets affected by this drug.