Iron as a critical determinant for survival, oxidative stress, and infectivity of Leishmania parasites
- 1ICMR-RM NIHR, Agamkuan, Patna
Abstract
Iron is an essential for all living organisms, including humans, and is present in RBCs & other iron-binding proteins that play crucial roles in oxygen transport, DNA synthesis & electron transport. Similarly, iron also plays a critical role in parasite biology. The unicellular Leishmania parasites scavenge essential iron inside host macrophages. We investigated the impact of iron on parasite growth, apoptosis, oxidative stress, and the expression of proteins involved in ROS, thiol metabolism, Fe-S clusters, and infectivity in macrophages. Our findings revealed that optimum iron concentrations promote parasite proliferation, whereas higher levels induce toxicity, leading to DNA fragmentation and caspase-like activity. Iron supplementation enhances parasite tolerance to oxidative stress by decreasing intracellular ROS and increasing total intracellular thiol content in a concentration-dependent manner. However, iron depletion increases ROS levels and decreases total thiol content in a concentration-dependent manner, which disrupts redox homeostasis. To support our finding, we further exposed these treated parasites to menadione, which supports that iron-supplemented cells can better survive under oxidative stress than the depleted cells. Furthermore, extra iron availability increases the expression of key metabolic proteins, Fe-S clusters (Nbp35, Frataxin, IScU) and thiol metabolism (TryS, TryR, CS, SAT, cTXN, cTXNPx), while under iron-depleted conditions these proteins were downregulated except frataxin. In vitro infectivity demonstrated that iron supplementation enhances parasite infectivity, while iron depletion impairs percentage infectivity. Our study demonstrates the roles of iron in the survival, redox regulation, and virulence of L. donovani, which can correlate with the role of cellular iron homeostasis in VL pathogenesis.
Related
- Leishmania-infected human dendritic cells clear their intracellular parasites by a mechanism involving the cytolytic effector molecules granzyme B and granulysin
- Active transcriptome remodeling underlies antimony-induced drug tolerance in persister-like Leishmania parasites
- Placentas from healthy women living in a cutaneous leishmaniasis endemic region in Mexico harbor Leishmania mexicana parasites: Potential implications for pregnancy and neonatal outcomes
- Blackcaps (Sylvia atricapilla) with blood parasites have impaired oxidative status during autumn migration
- The CXCL12γ/ACKR3 Axis Is a Critical Determinant of Myocardial Angiogenesis and Functional Recovery After Infarction
BibTeX
@misc{priydarshni2026iron,
title = {{Iron as a critical determinant for survival, oxidative stress, and infectivity of Leishmania parasites}},
author = {P. Priydarshni and A. Zaidi and P. Gupta and V. Ali},
howpublished = {bioRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.29.762707},
url = {https://www.biorxiv.org/content/10.64898/2026.10.29.762707v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - Iron as a critical determinant for survival, oxidative stress, and infectivity of Leishmania parasites
AU - P. Priydarshni
AU - A. Zaidi
AU - P. Gupta
AU - V. Ali
PY - 2026
DA - 2026/10/29
PB - bioRxiv
DO - 10.64898/2026.10.29.762707
UR - https://www.biorxiv.org/content/10.64898/2026.10.29.762707v1
AB - Iron is an essential for all living organisms, including humans, and is present in RBCs & other iron-binding proteins that play crucial roles in oxygen transport, DNA synthesis & electron transport. Similarly, iron also plays a critical role in parasite biology. The unicellular Leishmania parasites scavenge essential iron inside host macrophages. We investigated the impact of iron on parasite growth, apoptosis, oxidative stress, and the expression of proteins involved in ROS, thiol metabolism, Fe-S clusters, and infectivity in macrophages. Our findings revealed that optimum iron concentrations promote parasite proliferation, whereas higher levels induce toxicity, leading to DNA fragmentation and caspase-like activity. Iron supplementation enhances parasite tolerance to oxidative stress by decreasing intracellular ROS and increasing total intracellular thiol content in a concentration-dependent manner. However, iron depletion increases ROS levels and decreases total thiol content in a concentration-dependent manner, which disrupts redox homeostasis. To support our finding, we further exposed these treated parasites to menadione, which supports that iron-supplemented cells can better survive under oxidative stress than the depleted cells. Furthermore, extra iron availability increases the expression of key metabolic proteins, Fe-S clusters (Nbp35, Frataxin, IScU) and thiol metabolism (TryS, TryR, CS, SAT, cTXN, cTXNPx), while under iron-depleted conditions these proteins were downregulated except frataxin. In vitro infectivity demonstrated that iron supplementation enhances parasite infectivity, while iron depletion impairs percentage infectivity. Our study demonstrates the roles of iron in the survival, redox regulation, and virulence of L. donovani, which can correlate with the role of cellular iron homeostasis in VL pathogenesis.
ER -