SUMMARY Determining the composition of protein complexes is an essential step towards understanding the cell as an integrated system. Using co-affinity purification coupled to mass spectrometry analysis, we examined protein associations involving nearly five thousand individual, FLAG-HA epitope-tagged Drosophila proteins. Stringent analysis of these data, based on a novel statistical framework to define individual protein-protein interactions, led to the generation of a Drosophila Protein interaction Map (DPiM) encompassing 556 protein complexes. The high quality of DPiM and its usefulness as a paradigm for metazoan proteomes is apparent from the recovery of many known complexes, significant enrichment for shared functional attributes and validation in human cells. DPiM defines potential novel members for several important protein complexes and assigns functional links to 586 protein-coding genes lacking previous experimental annotation. DPiM represents, to our knowledge, the largest metazoan protein complex map and provides a valuable resource for analysis of protein complex evolution.
The authors note that in the abstract, lines 22-26, "To our knowledge, these results provide the first molecular insights into the secretome of P. destructans, and identify serine endopeptidases that have the clear potential to facilitate tissue invasion and pathogenesis in the mammalian host" were modified to correct an editorial oversight that occurred during the revision of the manuscript. The sentence has been corrected to read "These results provide molecular insights into the secretome of P. destructans, and identify serine endopeptidases that have the clear potential to facilitate tissue invasion and pathogenesis in the mammalian host." We apologize for this oversight.Also in the significance statement, lines 1-3, "To our knowledge, this work is the first to identify molecular factors produced by the fungus Pseudogymnoascus destructans, the causative agent of white-nose syndrome in bats" has similarly been corrected to read "This work identifies molecular factors produced by the fungus Pseudogymnoascus destructans, the causative agent of white-nose syndrome in bats."The online version has been corrected.www.pnas.org/cgi
Research on human fungal pathogens has historically taken a backseat to other infectious diseases, perhaps due to a common misperception that fungi largely cause superficial infections [1]. In reality, fungi can be life-threatening to those who become immunocompromised during medical procedures or through conditions such as HIV and diabetes. Invasive fungal infections are estimated to kill over 1 million people every year, with mortality rates reaching 50% [2]. Significant challenges to the treatment of fungal infections include the limited availability of antifungals and the innate ability of fungi to rapidly evolve and adapt to fluctuating conditions. This adaptive ability is partially driven by extensive genomic plasticity, with many species acquiring diverse ploidy states, chromosomal rearrangements, and point mutations during host colonization [3-8]. Genetic plasticity enables rapid increases in virulence and antifungal drug resistance, which often translate to poor disease outcomes. Short-term evolution (microevolution) strategies in fungal pathogens are therefore essential for environmental adaptation in the mammalian host, and their study can inform adaptive mechanisms in other eukaryotes. Ploidy shifts enable rapid fitness jumps under stressful conditions Many clinically relevant fungi display dynamic changes in ploidy, including both karyotypic variations (number of sets of chromosomes) as well as aneuploidy (imbalance in chromosome copy number). Some fungal pathogens exist as stable haploid, diploid, or polyploid cells, but ploidy can change upon shifting conditions. Alterations in baseline ploidy have been described for some of the most prevalent genera (Candida, Cryptococcus, and Aspergillus) and are often selected for in the host or during antifungal treatment. Extra chromosomes are common in isolates from human infections [5, 6, 8, 9] and after passage through mammalian hosts during experimental microevolution [10-12]. Under nutrient starvation, Candida albicans isolates can favor either near-haploid or near-diploid states, indicating that karyotypic reduction can provide an efficient adaptive route in some conditions [13]. Aneuploidy is also common in C. albicans and in Cryptococcus neoformans lineages and has been linked to increased virulence and drug resistance [14] [15]. Chromosomal duplication can mediate adaptation through gene dosage, as transcript levels are often proportional to gene copy number [16]. This can be seen in both C. albicans and Cryptococcus species, for which antifungal treatment selects for increased copies of chromosomes or chromosomal segments containing drug targets and/or efflux pumps. Thus, clinical isolates of Cryptococcus lineages VNI and VGI that persisted during fluconazole therapy were frequently disomic for chromosome 1 [5]. Analogous in vitro fluconazole treatment of Cryptococcus lineages VNI and VNIV selected for disomy of
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.