Ironing out the Details: Exploring the Role of Iron and Heme in Blood-Sucking Arthropods

Whiten, Shavonn Reezale; Eggleston, Heather; Adelman, Zach N.

doi:10.3389/fphys.2017.01134

Cited by 44 publications

(41 citation statements)

References 161 publications

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“…Hemoglobin remarkably attenuated the overproduction of ROS and NO, reverted mitochondrial membrane potential, and repressed caspase-3/7 (65). It is possible that the hemin/iron from degraded hemoglobin can immediately be transported into cells and incorporated to some of the heme-containing antioxidative enzymes (such as heme-containing catalases) when bacteria suffer the crisis of strong reactive oxygen radicals (42, 66). Similarly, some of the non-heme proteins (with iron as the cofactor) can remove the ROS (66).…”

Section: Discussionmentioning

confidence: 99%

Elizabethkingia anophelisresponse to iron stress: physiologic, genomic, and transcriptomic analyses

Chen

Johnson

et al. 2019

Preprint

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28Elizabethkingia anophelis bacteria encounter fluxes of iron in the midgut of mosquitoes, 29where they live as symbionts. They also establish bacteremia with severe clinical 30 manifestations in humans, and live in water service lines in hospitals. In this study, we 31 investigated the global gene expression responses of E. anophelis to iron fluxes in the midgut 32 of female Anopheles stephensi mosquitoes fed sucrose or blood, and in iron-poor or iron-rich 33 culture conditions. Of 3,686 transcripts revealed by RNAseq technology, 218 were upregulated 34 while 112 were down-regulated under iron-poor conditions. Most of these differentially 35 expressed genes (DEGs) were enriched in functional groups assigned within "biological 36 process," "cell component" and "molecular function" categories. E. anophelis possessed 4 37 iron/heme acquisition systems. Hemolysin gene expression was significantly repressed when 38 cells were grown under iron-rich or high temperature (37℃) conditions. Furthermore, 39 hemolysin gene expression was down-regulated after a blood meal, indicating that E. anophelis 40 cells responded to excess iron and its associated physiological stress by limiting iron loading. 41By contrast, genes encoding respiratory chain proteins were up-regulated under iron-rich 42 conditions, allowing these iron-containing proteins to chelate intracellular free iron. In vivo 43 studies showed that growth of E. anophelis cells increased 3-fold in blood-fed mosquitoes over 44 those in sucrose-fed ones. Deletion of aerobactin synthesis genes led to impaired cell growth 45 in both iron-rich and iron-poor media. Mutants showed more susceptibility to H 2 O 2 toxicity 46 and less biofilm formation than did wild-type cells. Mosquitoes with E. anophelis 47 experimentally colonized in their guts produced more eggs than did those treated with 48 erythromycin or left unmanipulated, as controls. Results reveal that E. anophelis bacteria 49 respond to varying iron concentration in the mosquito gut, harvest iron while fending off iron-50 associated stress, contribute to lysis of red blood cells, and positively influence mosquito host 51 fecundity. 52

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Section: Discussionmentioning

confidence: 99%

Elizabethkingia anophelisresponse to iron stress: physiologic, genomic, and transcriptomic analyses

Chen

Johnson

et al. 2019

Preprint

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“…aegypti midgut PM, our findings provide a foundation for future studies which are needed to better understand the physiological role of the PM after adult female bloodfeeding. While further strides have been taken to determine physiological function and importance of the PM in other hematophagous arthropods [ 52 , 55 , 61 ], reverse genetic analyses (RNAi mediated knockdown) are needed to confirm physiological function for known and putative Ae . aegypti PM proteins [ 61 ].…”

Section: Discussionmentioning

confidence: 99%

“…While further strides have been taken to determine physiological function and importance of the PM in other hematophagous arthropods [ 52 , 55 , 61 ], reverse genetic analyses (RNAi mediated knockdown) are needed to confirm physiological function for known and putative Ae . aegypti PM proteins [ 61 ]. Likewise, in vitro heme-binding assays are needed to confirm heme-binding for known and putative PM proteins.…”

Section: Discussionmentioning

confidence: 99%

Characterization of the adult Aedes aegypti early midgut peritrophic matrix proteome using LC-MS

et al. 2018

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The Aedes aegypti mosquito is the principal vector of arboviruses such as dengue, chikungunya, yellow fever, and Zika virus. These arboviruses are transmitted during adult female mosquito bloodfeeding. While these viruses must transverse the midgut to replicate, the blood meal must also reach the midgut to be digested, absorbed, or excreted, as aggregation of blood meal metabolites can be toxic to the female mosquito midgut. The midgut peritrophic matrix (PM), a semipermeable extracellular layer comprised of chitin fibrils, glycoproteins, and proteoglycans, is one such mechanism of protection for the mosquito midgut. However, this structure has not been characterized for adult female Ae. aegypti. We conducted a mass spectrometry based proteomic analysis to identify proteins that comprise or are associated with the adult female Ae. aegypti early midgut PM. Altogether, 474 unique proteins were identified, with 115 predicted as secreted. GO-term enrichment analysis revealed an abundance of serine-type proteases and several known and novel intestinal mucins. In addition, approximately 10% of the peptides identified corresponded to known salivary proteins, indicating Ae. aegypti mosquitoes extensively swallow their own salivary secretions. However, the physiological relevance of this remains unclear, and further studies are needed to determine PM proteins integral for midgut protection from blood meal derived toxicity and pathogen protection. Finally, we describe substantial discordance between previously described transcriptionally changes observed in the midgut in response to a bloodmeal and the presence of the corresponding protein in the PM. Data are available via ProteomeXchange with identifier PXD007627.

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“…Adapting to this peculiar diet for example requires dealing with the following: 1) the excess of liquid resulting from blood ingestion that is conveyed to the bladder through active transport of water ( Breidenstein 1982 ; Harlow and Braun 1997 ), 2) the potential toxicity of iron through its efficient sequestration in the intestinal epithelium both limiting its absorption and minimizing unnecessary losses ( Morton and Wimsat 1980 ; Morton and Janning 1982 ), and 3) the high protein content of the blood meal that results in higher urea production and increased renal activity ( Singer 2002 ). Given the ATP-dependent nature of active transport and the oxidative conditions created, for example, by the high amount of iron in blood ( Whiten et al 2018 ), these adaptations can be expected to have direct and indirect consequences on both mitochondrial physiology and the evolution of mitochondrial DNA. First, the increase in energy production is fulfilled through different mechanisms including regulation of the expression of mitochondrial proteins ( Mehrabian et al.…”

Section: Introductionmentioning

confidence: 99%

In Cold Blood: Compositional Bias and Positive Selection Drive the High Evolutionary Rate of Vampire Bats Mitochondrial Genomes

Botero-Castro

Tilak

Justy

et al. 2018

Genome Biology and Evolution

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Mitochondrial genomes of animals have long been considered to evolve under the action of purifying selection. Nevertheless, there is increasing evidence that they can also undergo episodes of positive selection in response to shifts in physiological or environmental demands. Vampire bats experienced such a shift, as they are the only mammals feeding exclusively on blood and possessing anatomical adaptations to deal with the associated physiological requirements (e.g., ingestion of high amounts of liquid water and iron). We sequenced eight new chiropteran mitogenomes including two species of vampire bats, five representatives of other lineages of phyllostomids and one close outgroup. Conducting detailed comparative mitogenomic analyses, we found evidence for accelerated evolutionary rates at the nucleotide and amino acid levels in vampires. Moreover, the mitogenomes of vampire bats are characterized by an increased cytosine (C) content mirrored by a decrease in thymine (T) compared with other chiropterans. Proteins encoded by the vampire bat mitogenomes also exhibit a significant increase in threonine (Thr) and slight reductions in frequency of the hydrophobic residues isoleucine (Ile), valine (Val), methionine (Met), and phenylalanine (Phe). We show that these peculiar substitution patterns can be explained by the co-occurrence of both neutral (mutational bias) and adaptive (positive selection) processes. We propose that vampire bat mitogenomes may have been impacted by selection on mitochondrial proteins to accommodate the metabolism and nutritional qualities of blood meals.

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Ironing out the Details: Exploring the Role of Iron and Heme in Blood-Sucking Arthropods

Cited by 44 publications

References 161 publications

Elizabethkingia anophelisresponse to iron stress: physiologic, genomic, and transcriptomic analyses

Elizabethkingia anophelisresponse to iron stress: physiologic, genomic, and transcriptomic analyses

Characterization of the adult Aedes aegypti early midgut peritrophic matrix proteome using LC-MS

In Cold Blood: Compositional Bias and Positive Selection Drive the High Evolutionary Rate of Vampire Bats Mitochondrial Genomes

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