Heme metabolism in Strigomonas culicis: Implications of H 2 O 2 resistance induction and symbiont elimination.

Autor: Bombaça ACS; Laboratório de Biologia Celular, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil; Laboratório de Doenças Parasitárias, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil., Caminha MA; Laboratório de Biologia Celular, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil; Laboratório de Toxinologia, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro Brazil., Barbosa JMC; Laboratório de Biologia Celular, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil., Pedra-Rezende Y; Laboratório de Biologia Celular, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil; Laboratório de Toxinologia, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro Brazil., Ennes-Vidal V; Laboratório de Doenças Parasitárias, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil., Brunoro GVF; Research and Development in Biotechnology, Blau Farmacêutica S/A, São Paulo, Brazil., Archanjo BS; Divisão de Metrologia de Materiais, Instituto Nacional de Metrologia, Qualidade e Tecnologia (Inmetro), Duque de Caxias, Brazil., d'Avila CM; Laboratório de Doenças Parasitárias, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil., Valente RH; Laboratório de Toxinologia, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro Brazil., Menna-Barreto RFS; Laboratório de Biologia Celular, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil. Electronic address: rubemsadok@gmail.com.
Jazyk: angličtina
Zdroj: The Journal of biological chemistry [J Biol Chem] 2024 Sep; Vol. 300 (9), pp. 107692. Date of Electronic Publication: 2024 Aug 17.
DOI: 10.1016/j.jbc.2024.107692
Abstrakt: Monoxenous trypanosomatid Strigomonas culicis harbors an endosymbiotic bacterium, which enables the protozoa to survive without heme supplementation. The impact of H 2 O 2 resistance and symbiont elimination on intracellular heme and Fe 2+ availability was analyzed through a comparison of WT strain with both WT H 2 O 2 -resistant (WTR) and aposymbiotic (Apo) protozoa. The relative quantification of the heme biosynthetic pathway through label-free parallel reaction monitoring targeted mass spectrometry revealed that H 2 O 2 resistance does not influence the abundance of tryptic peptides. However, the Apo strain showed increased coproporphyrinogen III oxidase and ferrochelatase levels. A putative ferrous iron transporter, homologous to LIT1 and TcIT from Leishmania major and Trypanosoma cruzi, was identified for the first time. Label-free parallel reaction monitoring targeted mass spectrometry also showed that S. culicis Iron Transporter (ScIT) increased 1.6- and 16.4-fold in WTR and Apo strains compared to WT. Accordingly, antibody-mediated blockage of ScIT decreased by 28.0% and 40.0% intracellular Fe 2+ concentration in both WTR and Apo strains, whereas no effect was detected in WT. In a heme-depleted medium, adding 10 μM hemin decreased ScIT transcript levels in Apo, whereas 10 μM PPIX, the substrate of ferrochelatase, increased intracellular Fe 2+ concentration and ferric iron reduction. Overall, the data suggest mechanisms dependent on de novo heme synthesis (and its substrates) in the Apo strain to overcome reduced heme availability. Given the importance of heme and Fe 2+ as cofactors in metabolic pathways, including oxidative phosphorylation and antioxidant systems, this study provides novel mechanistic insights associated with H 2 O 2 resistance in S. culicis.
Competing Interests: Conflict of interest The authors declare that they have no conflicts of interest with the contents of this article.
(Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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