Fungal and host protein persulfidation are functionally correlated and modulate both virulence and antifungal response

Aspergillus fumigatus is a human fungal pathogen that can cause devastating pulmonary infections, termed “aspergilloses,” in individuals suffering immune imbalances or underlying lung conditions. As rapid adaptation to stress is crucial for the outcome of the host–pathogen interplay, here we investigated the role of the versatile posttranslational modification (PTM) persulfidation for both fungal virulence and antifungal host defense. We show that an A. fumigatus mutant with low persulfidation levels is more susceptible to host-mediated killing and displays reduced virulence in murine models of infection. Additionally, we found that a single nucleotide polymorphism (SNP) in the human gene encoding cystathionine γ-lyase (CTH) causes a reduction in cellular persulfidation and correlates with a predisposition of hematopoietic stem cell transplant recipients to invasive pulmonary aspergillosis (IPA), as correct levels of persulfidation are required for optimal antifungal activity of recipients’ lung resident host cells. Importantly, the levels of host persulfidation determine the levels of fungal persulfidation, ultimately reflecting a host–pathogen functional correlation and highlighting a potential new therapeutic target for the treatment of aspergillosis.

This study reveals that the post-translational modification persulfidation is important for both fungal virulence and the host antifungal response. The level of persulfidation in the host, which correlates with its antifungal potency, impacts the level required in the fungus to counteract host attack, reflecting a functional correlation. Thus modulating persulfidation may be a promising strategy to target both pathogens and immune responses.     

Toxicity of lead and zinc to developing mussel and sea urchin embryos: Critical tissue residues and effects of dissolved organic matter and salinity

Lead (Pb) EC50 values in the very sensitive early development phases (48–72 h post-fertilization) of the mussels Mytilus galloprovincialis and Mytilus trossolus and sea urchin Strongylocentrotus purpuratus in 100% sea water were: M. trossolus — 45 (95% C.I. = 22–72) μg L^− 1; M. galloprovincialis — 63 (36–94) μg L^− 1; S. purpuratus — 74 (50–101) μg L^− 1. Salinity thresholds for normal development varied: M. trossolus > 21 ppt; M. galloprovincialis > 28 ppt; S. purpuratus ≥ 30 ppt. Addition of two spectroscopically distinct dissolved organic matters (DOM) from fresh water (Nordic Reservoir) and sea water (Inshore) moderately decreased the toxicity of Pb to both mussels, but not in a concentration-dependent fashion, with only an approximate doubling of EC50 over the range of 1.4–11.2 mg C L^− 1. Independent Pb binding capacity determinations for DOC explained the lack of a relationship between DOM concentration and toxicity. Salinity had no effect on Pb toxicity down to 21 ppt in M. trossolus, and low salinity (21 ppt) did not enhance the protective effect of DOC. Both DOMs increased the toxicity of Pb in developing sea urchin embryos, in contrast to mussels. Relative to Pb, the organisms were 6–9 fold less sensitive to Zn on a molar basis in 100% seawater with the following Zn EC50s: M. trossolus — 135 (103–170) μg L^− 1; M. galloprovincialis — 172 (126–227) μg L^− 1, S. purpuratus — 151 (129–177) μg L^− 1. Nordic Reservoir and Inshore DOM (2–12 mg C L^− 1) had no significant effect on Zn toxicity to mussels, in accord with voltammetry data showing an absence of any strong ligand binding for Zn by DOMs. As with Pb, DOMs increased Zn toxicity to urchin larvae. Critical Tissue Residues (CTR) based on whole body concentrations of Pb and Zn were determined for M. galloprovincialis at 48 h and S. purpuratus at 72 h. The median lethal CTR values (LA50s), useful parameters for development of saltwater Biotic Ligand Models (BLMs), were approximately 4-fold higher on a molar basis for Zn than for Pb. The latter were not altered by DOM exposure, despite increased EC50 values, in accord with the tenets of the BLM.     

Enhancer viruses for combinatorial cell-subclass-specific labeling

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Biogeographic history of subterranean isopods from groundwater calcrete islands in Western Australia

Groundwater calcretes in arid central Western Australia contain a diverse invertebrate groundwater fauna (stygofauna). Surveys have uncovered a diverse oniscidean isopod subterranean fauna above the water table (troglofauna), including species of a recently described genus Paraplatyarthrus. The aim of this study was to investigate the biogeographic history of Paraplatyarthrus and the timing of transitions from surface to subterranean habitats. Phylogenetic relationships among the isopod troglofauna from 11 groundwater calcretes along three palaeodrainage systems were assessed using one mitochondrial gene, cytochrome c oxidase subunit 1 (COI), and two nuclear markers, lysyl‐tRNA synthetase (LysRS) and 18S rRNA (18S) genes. Phylogenetic analyses revealed multiple sister lineage relationships between troglophile and troglobite lineages and evidence for divergent mtDNA lineages within species, providing a range of nodes for dating evolutionary transitions from surface to subterranean habitats. Relaxed molecular clock analyses provided evidence that evolutionary transitions from surface to subterranean environments took place between 13.3 and 1.75 million years ago, coinciding with the onset of aridification of Australia from the late Tertiary. In cases where groundwater calcretes contained multiple species, the taxa were not closely related phylogenetically, suggesting that these calcretes were independently colonised by multiple ancestral species. The study further confirmed the role of late/post‐Miocene aridification as a key driver of the evolution of subterranean invertebrates in the calcrete islands of Western Australia, supporting the climatic relict hypothesis. Troglobites most likely evolved from the troglophile ancestors that were capable of dispersal among, and active colonisation of, calcretes.     

Mechanisms regulating phosphatase specificity and the removal of individual phosphorylation sites during mitotic exit

Entry into mitosis is driven by the activity of kinases, which phosphorylate over 7000 proteins on multiple sites. For cells to exit mitosis and segregate their genome correctly, these phosphorylations must be removed in a specific temporal order. This raises a critical and important question: how are specific phosphorylation sites on an individual protein removed? Traditionally, the temporal order of dephosphorylation was attributed to decreasing kinase activity. However, recent evidence in human cells has identified unique patterns of dephosphorylation during mammalian mitotic exit that cannot be fully explained by the loss of kinase activity. This suggests that specificity is determined in part by phosphatases. In this review, we explore how the physicochemical properties of an individual phosphosite and its surrounding amino acids can affect interactions with a phosphatase. These positive and negative interactions in turn help determine the specific pattern of dephosphorylation required for correct mitotic exit.     

A northward shift of range margins in British Odonata

Many species are predicted to shift their ranges to higher latitudes and altitudes in response to climate warming. This study presents evidence for 37 species of nonmigratory British dragonflies and damselflies shifting northwards at their range margins over the past 40 years, seemingly as a result of climate change. This response by an exemplar group of insects associated with fresh water, parallels polewards range changes observed in terrestrial invertebrates and other taxa.