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Abstract Iron is essential to life, but surprisingly little is known about how iron is managed in nonvertebrate animals. In mammals, the well‐characterizedtransferrinsbind iron and are involved in iron transport or immunity, whereas other members of thetransferrinfamily do not have a role in iron homeostasis. In insects, the functions oftransferrinsare still poorly understood. The goals of this project were to identify thetransferringenes in a diverse set of insect species, resolve the evolutionary relationships among these genes, and predict which of thetransferrinsare likely to have a role in iron homeostasis. Our phylogenetic analysis oftransferrinsfrom 16 orders of insects and two orders of noninsect hexapods demonstrated that there are four orthologous groups of insecttransferrins. Our analysis suggests thattransferrin 2arose prior to the origin of insects, andtransferrins 1,3, and4arose early in insect evolution. Primary sequence analysis of each of the insecttransferrinswas used to predict signal peptides, carboxyl‐terminal transmembrane regions, GPI‐anchors, and iron binding. Based on this analysis, we suggest thattransferrins 2,3, and4are unlikely to play a major role in iron homeostasis. In contrast, thetransferrin 1orthologs are predicted to be secreted, soluble, iron‐binding proteins. We conclude thattransferrin 1orthologs are the most likely to play an important role in iron homeostasis. Interestingly, it appears that the louse, aphid, and thrips lineages have lost thetransferrin 1gene and, thus, have evolved to manage iron withouttransferrins.
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Point Mutations in TbpA Abrogate Human Transferrin Binding in Neisseria gonorrhoeae
ABSTRACT TonB-dependent transporters (TDTs) are essential proteins for metal acquisition, an important step in the growth and pathogenesis of many pathogens, including Neisseria gonorrhoeae , the causative agent of gonorrhea. There is currently no available vaccine for gonorrhea; TDTs are being investigated as vaccine candidates because they are highly conserved and expressed in vivo . Transferrin binding protein A (TbpA) is an essential virulence factor in the initiation of experimental infection in human males and functions by acquiring iron upon binding to host transferrin (human transferrin [hTf]). The loop 3 helix (L3H) is a helix finger that inserts into the hTf C-lobe and is required for hTf binding and subsequent iron acquisition. This study identified and characterized the first TbpA single-point substitutions resulting in significantly decreased hTf binding and iron acquisition, suggesting that the helix structure is more important than charge for hTf binding and utilization. The tbpA D355P Δ tbpB and tbpA A356P Δ tbpB mutants demonstrated significantly reduced hTf binding and impaired iron uptake from Fe-loaded hTf; however, only the tbpA A356P Δ tbpB mutant was able to grow when hTf was the sole source of iron. The expression of tbpB was able to restore function in all tbpA mutants. These results implicate both D355 and A356 in the key binding, extraction, and uptake functions of gonococcal TbpA.
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- PAR ID:
- 10398100
- Editor(s):
- Bäumler, Andreas J.
- Date Published:
- Journal Name:
- Infection and Immunity
- Volume:
- 90
- Issue:
- 11
- ISSN:
- 0019-9567
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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- Free Publicly Accessible Full Text
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Accepted Manuscript1.0
- Journal Article:
- https://doi.org/10.1128/iai.00414-22
