Explore the vast range of titles available.

Submarines and spacecraft share several features that may promote the presence of fungi, including recirculated ventilation systems, moist areas, and close-quarters living. In this article, we introduce the idea of \"submarine mycology\" and explore how research on submarine fungi can inform the emerging field of astromycology. We highlight parallels in the fungal species present in both environments, while also noting key differences such as radiation exposure and microgravity. Arguing that submarines offer valuable lessons for spaceflight, we advocate for renewed research using modern genetic tools to characterize submarine fungi.

Human cytomegalovirus (HCMV) is a master of immune evasion and a potent modulator of the human immune system. The best-characterized mechanism employed by HCMV to suppress host immunity is the production of a viral interleukin-10 homolog (CMVIL-10). While CMVIL-10 is known to suppress immune responses and promote viral persistence, its capacity to promote increased susceptibility to co-infecting pathogens like Aspergillus fumigatus remains unknown. Therefore, we studied the impact of wild-type (WT) HCMV (strain TB40), a CMVIL-10-deficient HCMV mutant (ΔUL111A), and recombinant CMVIL-10 on the immune activity of monocyte-derived dendritic cells (moDCs) during co-infection with A. fumigatus. Using a combination of transcriptomic and phenotypic readouts, our data revealed a strong and time-dependent immuno-paralytic effect of HCMV by suppressing pathogen recognition pathways, cytokine production, DC maturation, and expression of genes that are essential for host defense and tissue repair. Although infection with ΔUL111A lacking CMVIL-10 led to stronger expression of type I interferons, IFN-γ-inducible chemokines, and proinflammatory cytokines than WT infection, interference with antifungal immune defense and fungal clearance during co-infection was largely similar between both strains. The limited effect of CMVIL-10 on antifungal immune defense persisted even after prolonged pre-exposure of DCs to the recombinant virokine. In summary, although CMVIL-10 contributes to shaping an anti-inflammatory environment, HCMV’s suppression of antifungal immunity appears to be multifactorial, with CMVIL-10 alone playing a rather subtle role in altering DC responses to A. fumigatus during viral-fungal co-infection.IMPORTANCEHuman cytomegalovirus (HCMV) is a highly prevalent herpesvirus that establishes lifelong latency and frequently reactivates in immunocompromised individuals, including hematopoietic stem cell transplant recipients. Reactivation not only causes direct disease but also increases the risk of secondary infections, such as invasive pulmonary aspergillosis caused by Aspergillus fumigatus. Specifically, studies estimated that about 6%–25% of critically ill HCMV-positive patients develop HCMV-associated pulmonary aspergillosis. However, the mechanisms by which HCMV creates a permissive environment for fungal superinfection remain poorly understood. HCMV encodes a viral homolog of interleukin-10 (CMVIL-10), which mimics host IL-10 and elicits potent immunomodulatory activity. Here, we show that CMVIL-10 dampens specific anti-viral responses, DC activation, and cytokine signaling. However, HCMV-mediated impairment of fungal control in co-infection settings occurred largely independent of CMVIL-10 expression. These findings suggest that HCMV undermines antifungal defenses through multifactorial mechanisms beyond CMVIL-10, highlighting the need for targeted strategies to restore immune function in high-risk patients.

Fungal infections in the lungs are lethal complications for those with compromised immune systems and have limited treatment strategies available. These options are restricted further by the increased prevalence of treatment-resistant fungi. Many studies focus on how our immune systems respond to these pathogens, yet airway epithelial cells remain an understudied component of fungal infections in the lungs. Here, the authors provide a transcriptional analysis of primary human airway epithelial cells stimulated by two distinct fungal pathogens, Aspergillus fumigatus and Coccidioides posadasii . These data will enable further mechanistic studies of the contribution of the airway epithelium to initial host responses and represent a powerful new resource for future investigations.

Pneumocystis species are obligate fungal pathogens and major causes of pneumonia in immunocompromised individuals. However, their strict dependence on the mammalian lung environment has precluded the development of genetic manipulation systems, limiting our ability to interrogate gene function, study antifungal resistance mechanisms, or validate therapeutic targets. Here, we report the first successful approach for stable transformation and CRISPR/Cas9-based genome editing of Pneumocystis murina , achieved through in vivo delivery of engineered extracellular vesicles containing plasmid DNA and encoding CRISPR/Cas9 components. We demonstrate sustained transgene expression and precise modification of the dhps locus via homology-directed repair. This modular, scalable platform overcomes a long-standing barrier in the field and establishes a foundation for functional genomics in Pneumocystis and other obligate, host-adapted microbes.

Candida albicans is a commensal yeast that is a common component of the gastrointestinal (GI) microbiome of humans. C. albicans has been shown to bloom in the GI tract of individuals with alcohol use disorder (AUD) and can promote and increase the severity of alcoholic liver disease. However, the effects of C. albicans blooms on the host in the context of AUD or AUD-related phenotypes, such as ethanol preference, have been unstudied. In this work, we report a reduction in ethanol consumption and preference in mice colonized with C. albicans. C. albicans-colonized mice exhibited elevated levels of serum prostaglandin E2 (PGE2), and the reduced ethanol preference was reversed by injection with antagonists of PGE2 receptors. Furthermore, injection of mice with a PGE2 derivative decreased their ethanol preference. These results show that PGE2 acting on its receptors prostaglandin E receptor 1 (EP1) and prostaglandin E receptor 2 (EP2) drives reduced ethanol preference in C. albicans-colonized mice. We also showed altered transcription of dopamine receptors in the dorsal striatum of C. albicans-colonized mice and more rapid acquisition of ethanol-conditioned taste aversion, suggesting alterations to reinforcement or aversion learning. Finally, C. albicans-colonized mice were more susceptible to ethanol-induced motor coordination impairment, showing significant alterations to the behavioral effects of ethanol. This study identifies a member of the fungal microbiome that alters ethanol preference and demonstrates a role for PGE2 signaling in these phenotypes.IMPORTANCECandida albicans is a commensal yeast that is found in the gut of most individuals. C. albicans has been shown to contribute to alcoholic liver disease. Outside of this, the impact of intestinal fungi on alcohol use disorder (AUD) had been unstudied. As AUD is a complex disorder characterized by high relapse rates and there are only three FDA-approved therapies for the maintenance of abstinence, it is important to study novel AUD contributors to find new therapeutic targets. Here, we show that an intestinal fungus, C. albicans, can alter mammalian ethanol consumption through an immune modulator, prostaglandin E2. The results highlight novel contributors to AUD-related phenotypes and further implicate the gut-brain axis in AUD. Future studies could lead to new therapeutic avenues for the treatment of AUD.

Cryptococcosis is a systemic fungal infection that causes approximately 1 million cases globally, leading to approximately 625,000 annual deaths. Two species are responsible for the majority of cases, Cryptococcus neoformans and Cryptococcus gattii . C. neoformans usually causes disease in immunosuppressed hosts, whereas C. gattii can infect and cause disease in immunocompetent hosts. The capsule of Cryptococcus spp. is one of its major virulence factors, due to its immunomodulation abilities. The capsule is composed of three major different molecules: glucuronoxylomannan (GXM), galactoxylomannan (GalXM), and mannoproteins. GXM is composed of six different structures called motifs. The exact mechanism and structures associated with its immunomodulation are still not well elucidated. Here, we looked at different immune responses based on the capsule composition. Our results strongly suggest that the capsule motif composition can affect the virulence, pathogenicity, and immunomodulatory capabilities of the Cryptococcus capsule.

Conidia serve as the primary infectious units of Aspergillus fumigatus , the causative agent of aspergillosis. This study identifies CrpA, a cysteine-rich protein found on the conidial surface, as a crucial regulator of immune modulation and fungal virulence. Loss of CrpA (Δ crpA ) alters host immune responses, resulting in reduced production of proinflammatory cytokines and increased IL-10 levels in both murine macrophages and infected lungs. ΔcrpA conidia also stimulate elevated levels of prostaglandins PGE2 and PGD2. This immunomodulatory effect is dependent on eicosanoid signaling as the virulence of Δ crpA is restored in prostaglandin-deficient zebrafish larvae. CrpA directly modulates macrophage production of PGE2 and cytokines. Solid-state NMR analysis shows that Δ crpA conidia expose lower levels of β−1,3-glucan and chitin, suggesting that CrpA influences both cell wall composition and host pattern recognition receptor engagement. Δ crpA strains are avirulent in immunocompetent mice, and patients with invasive pulmonary aspergillosis exhibit elevated CrpA-specific IgG. These results highlight CrpA as a key virulence factor in A. fumigatus and a promising target for antifungal therapy.

Cryptococcus neoformans is a fungal pathogen that causes substantial morbidity and mortality in immunocompromised individuals. The initial infection begins in the lungs after exposure to inhaled spores, after which local immune cells respond by either killing or containing the fungal cells. Immunosuppression weakens the immune system and allows fungal cells in the lungs to escape through the circulatory system and invade the central nervous system and cause fatal disease. However, differences between fungal strains influence the severity of disease manifestation. Our group has previously described genetic differences that contribute to strain-specific disease manifestations. In this study, we expanded our analysis to investigate the proteomic differences between strains of C. neoformans to identify candidate proteins and pathways that contribute to disease manifestation. We found that latent infection differs significantly from lethal disease from both the host and pathogen proteomic perspectives and identified several fungal protein targets for future study.

Candida auris is an emerging fungal species, and several reports have recently identified C. auris in patients with vulvovaginal candidiasis (VVC), although few studies have investigated the relationship between C. auris and VVC or the associated host factors. Our study, using the VVC mouse model, confirmed persistent vaginal colonization by C. auris , especially clades I, III, and IV, along with reduced neutrophil infiltration and lower S100A8 secretion under interleukin-17A-deficient conditions. In addition, in vitro assays demonstrated enhanced C. auris adhesion to vaginal epithelial cells, especially microaerobic conditions imitating human vaginal microenvironments. Our findings suggest that C. auris exhibits strong vaginal tropism, and IL-17A plays a critical role in controlling C. auris -associated VVC.

Municipal solid waste (MSW) represents an inevitable by-product of human activity and a major crisis for communities across the globe. In recent times, the recycling of MSW has drawn attention as the process can add value through resources from the recovered waste materials and facilitates the process of circular economy. However, during the unprecedented coronavirus (COVID-19) outbreak, the risk of infection with the highly contagious virus has proven detrimental to the continuation of MSW as a valuable resource. The volume of waste, especially household waste, is higher; face masks, PPE (personal protective equipment), and hazardous materials such as batteries and empty chlorine bottles are examples of extra waste that have arisen during the pandemic. Various countries have set up initiatives for MSW management, including safety measurements for employees in the MSW management sector. The use of disinfectant prior to sorting waste, as well as storing waste for 9 days, may help to inactivate the COVID-19 virus, ensuring an appropriate safety level for MSW management. This work aimed at studying different MSW management strategies, specific challenges, and possible solutions for better understanding for those involved in waste management, in addition to providing a possible management strategy during and post-COVID-19 pandemic. Graphical abstract