Biology subjects

Emami, S. N.

Publications and source records attributed to Emami, S. N..

3 recordsLinked to original sources

bioRxiv2026

A Poly(rC)-Binding Protein Mediates Iron Delivery to Ferritin in Anopheles stephensi

Iron homeostasis is essential for both the Plasmodium parasite and its hosts, the mosquito and human; however, the molecular mechanisms governing intracellular iron trafficking remain poorly understood. In mammals, poly(rC)-binding proteins (PCBPs) function as major iron chaperones by delivering Fe2+ to ferritin and other iron-dependent proteins, yet their role in insects has not been investigated. Here, we provide the first structural and functional characterization of the PCBP from a major malaria vector, Anopheles stephensi. Comparative structural and evolutionary analyses showed that insect PCBPs are most closely related to human PCBP3. Coordinated expression and co-localization of AsPCBP with ferritin following blood feeding suggested a conserved role in mosquito iron homeostasis. Functional analyses demonstrated that KH2-KH3 linker and KH3 domain of PCBP, plays an important role in the AsPCBP-ferritin interaction and that deletion of these regions, unexpectedly increased ferritin binding affinity but impaired iron delivery, indicating that these regions are dispensable for complex formation but essential for efficient iron transfer. Collectively, our results identify PCBP as a key component of mosquito iron homeostasis that could be exploited for the development of novel antimalarial strategies.

biochemistry↗

bioRxiv2022

Single-cell transcriptomics to define Plasmodium falciparum stage-transition in the mosquito midgut

Malaria inflicts the highest rate of morbidity and mortality among the vector-borne diseases. The dramatic bottleneck of parasite numbers that occurs in the gut of the obligatory vector mosquito provides a promising target for novel control strategies. Using single-cell transcriptomics, we analyzed Plasmodium falciparum development in the mosquito gut, from unfertilized female gametes through the first 20 hours post blood feeding, including the zygote and ookinete stages. This study revealed the transcriptional trajectories of the ApiAP2 family of transcription factors, and of parasite stress genes in response to the harsh environment of the mosquito midgut. Further, employing structure-based functional predictions we found several upregulated genes predicted to encode intrinsically disordered proteins (IDPs), a category of proteins known for their importance in regulation of transcription, translation and protein-protein interactions. IDPs are known for their antigenic properties and may serve as suitable targets for antibody or peptide-based transmission suppression strategies.

microbiology↗

bioRxiv2018

Intersection of phosphate transport, oxidative stress and TOR signalling in Candida albicans virulence

Phosphate is an essential macronutrient required for cell growth and division. Pho84 is the major high-affinity cell-surface phosphate importer of Saccharomyces cerevisiae and a crucial element in the phosphate homeostatic system of this model yeast. We found that loss of Candida albicans Pho84 attenuated virulence in Drosophila and murine oropharyngeal and disseminated models of invasive infection, and conferred hypersensitivity to neutrophil killing. Susceptibility of cells lacking Pho84 to neutrophil attack depended on reactive oxygen species (ROS): pho84-/- cells were no more susceptible than wild type C. albicans to neutrophils from a patient with chronic granulomatous disease, or to those whose oxidative burst was pharmacologically inhibited or neutralized. pho84-/- mutants hyperactivated oxidative stress signalling. They accumulated intracellular ROS in the absence of extrinsic oxidative stress, in high as well as low ambient phosphate conditions. ROS accumulation correlated with diminished levels of the unique superoxide dismutase Sod3 in pho84-/- cells, while SOD3 overexpression from a conditional promoter substantially restored these cells oxidative stress resistance in vitro. Repression of SOD3 expression sharply increased their oxidative stress hypersensitivity. Neither of these oxidative stress management effects of manipulating SOD3 transcription was observed in PHO84 wild type cells. Sod3 levels were not the only factor driving oxidative stress effects on pho84-/- cells, though, because overexpressing SOD3 did not ameliorate these cells hypersensitivity to neutrophil killing ex vivo, indicating Pho84 has further roles in oxidative stress resistance and virulence. Measurement of cellular metal concentrations demonstrated that diminished Sod3 expression was not due to decreased import of its metal cofactor manganese, as predicted from the function of S. cerevisiae Pho84 as a low-affinity manganese transporter. Instead of a role of Pho84 in metal transport, we found its role in TORC1 activation to impact oxidative stress management: overexpression of the TORC1-activating GTPase Gtr1 relieved the Sod3 deficit and ROS excess in pho84-/- null mutant cells, though it did not suppress their hypersensitivity to neutrophil killing or hyphal growth defect. Pharmacologic inhibition of Pho84 by small molecules including the FDA-approved drug foscarnet also induced ROS accumulation. Inhibiting Pho84 could hence support host defenses by sensitizing C. albicans to oxidative stress.

microbiology↗