Involvement of tryparedoxin peroxidase (TryP) and trypanothione reductase (TryR) in antimony unresponsive of Leishmania tropica clinical isolates of Iran

Effect of Phlebotomus papatasi on the fitness, infectivity and antimony-resistance phenotype of antimony-resistant Leishmania major Mon-25

“…has been implicated in parasite-host interaction. Like other proteins in the glutathione/trypanothione-based redox system, this gene allows the reduction of Sb(V) to Sb(III) and is over-expressed in antimony-resistant parasites ( Denton et al, 2004 ; Nateghi-Rostami, Tasbihi & Darzi, 2022 ). However, these proteins have not yet been studied to understand their implication and specific role in the survival of Leishmania parasites during the vector phase of their life-cycle.…”

Antimony resistance and gene expression in Leishmania: spotlight on molecular and proteomic aspects

“…The TR protein augmentation was proportional to its activity, with a more than doubled mean activity in non-responders vs responders, in the clinical isolates of L. tropica from ACL patients (Nateghi-Rostami et al ., 2022). The high thiol levels observed in natural Sb-resistant L. donovani cells with concurrent amplification of TR and MRPA were not mediated by the γ -GCS (Mittal et al ., 2007).…”

“…Additionally, the TR expression was almost the same in between the Sb-unresponsive and -sensitive L. donovani clinical extracts, and it was suggested that TR had no clear role in Sb resistance in Leishmania (Nateghi-Rostami et al ., 2022). Studies conducted by Wyllie et al .…”

“…TDR1 was strikingly upregulated in the amastigotes than that of the promastigotes, and it was attributed to the TDR1-mediated reduction of Sb(V) to Sb(III), whereas promastigotes were prominently sensitive to Sb(V) than the amastigotes (Shaked-Mishant et al ., 2001; Denton et al ., 2004). All the MA non-responders in a study showed significantly elevated metabolic activity against hydrogen peroxide (H 2 O 2 ) compared to the lower activity seen in responders, which was in line with the elevated trypanothione peroxidase levels in non-responders (Nateghi-Rostami et al ., 2022). A 3–4-fold increased TDR expression was experienced in SSG-resistant parasites of L. donovani and L. tropica than in the sensitive line (Khanra et al ., 2022).…”

“…A several-fold augmented TryP protein levels were reported in Sb-resistant Leishmania, accompanied by activated H 2 O 2 metabolism as well as increased tolerance to exogenous H 2 O 2 than the respective sensitive or parental lines (Andrade and Murta, 2014). Moreover, the elevation of TryP was also accompanied by a significant (>2 times average) TR expression in the resistant extracts, with an emphasis on the synergistic interactions of proteins involved in thiol-metabolism in gaining Sb resistance (Nateghi-Rostami et al ., 2022). A 3 times TryP boost was observed in Sb-resistant L. tarentolae compared to that observed in lysates of revertant, along with a positive correlation to the subsequent peroxidase activity (Wyllie et al ., 2008).…”