ABSTRACT
Candida albicans stably colonizes humans but is the leading cause of hospital-acquired fungemia. Traditionally, masking immunogenic moieties has been viewed as a tactic for immune evasion. Here, we demonstrate that C. albicans blocks type I interferon (IFN-I) signaling via translocating an effector protein Cmi1 into host cells. Mechanistically, Cmi1 binds and inhibits TANK-binding kinase 1 (TBK1) to abrogate IFN-regulatory factor 3 (IRF3) phosphorylation, thereby suppressing the IFN-I cascade. Murine infection with a cmi1 mutant displays an exaggerated IFN-I response in both kidneys and bone-marrow-derived macrophages, leading to rapid fungal clearance and host survival. Remarkably, the lack of CMI1 compromises gut commensalism and increases IFN-I response in mouse colonic cells. These phenotypes of cmi1 are rescued by the depletion of IFN-I receptor. This work establishes the importance of TBK1 inhibition in fungal pathogenesis and reveals that a human commensal-pathogenic fungus significantly impacts host immunity during gut colonization and infection via delivering effector proteins into host cells.
ABSTRACT
Microplastics pose a severe threat to marine ecosystems; however, relevant mathematical modeling and analysis are lacking. This paper formulates two stoichiometric producer-grazer models to investigate the interactive effects of microplastics, nutrients, and light on population dynamics under different settings. One model incorporates optimal microplastic uptake and foraging behavior based on nutrient availability for natural settings, while the other model does not include foraging in laboratory settings. We establish the well-posedness of the models and examine their long-term behaviors. Our results reveal that in natural environments, producers and grazers exhibit higher sensitivity to microplastics, and the system may demonstrate bistability or tristability. Moreover, the influences of microplastics, nutrients, and light intensity are highly intertwined. The presence of microplastics amplifies the constraints on grazer growth related to food quality and quantity imposed by extreme light intensities, while elevated phosphorus input enhances the system's resistance to intense light conditions. Furthermore, higher environmental microplastic levels do not always imply elevated microplastic body burdens in organisms, as organisms are also influenced by nutrients and light. We also find that grazers are more vulnerable to microplastics, compared to producers. If producers can utilize microplastics for growth, the system displays significantly greater resilience to microplastics.
Subject(s)
Ecosystem , Water Pollutants, Chemical , Microplastics/toxicity , Plastics , Models, Theoretical , Light , Water Pollutants, Chemical/toxicity , Environmental MonitoringABSTRACT
With the continuous improvement of living standards and advancements in science and technology, composite materials with multiple functionalities are gaining high practical value in modern society. In this paper, we present a multifunctional conductive paper-based composite with electromagnetic (EMI) shielding, sensing, Joule heating, and antimicrobial properties. The composite is prepared by growing metallic silver nanoparticles inside the cellulose paper (CP) modified with polydopamine (PDA). The resulting CP@PDA@Ag (CPPA) composite has high conductivity and EMI shielding properties. Furthermore, CPPA composites demonstrate exceptional sensing, Joule heating, and antimicrobial properties. In addition, Vitrimer, a polymer with excellent cross-linked network structure, is introduced into CPPA composites to obtain CPPA-V intelligent electromagnetic shielding materials with shape memory function. These excellent properties show that the prepared multifunctional intelligent composite has exceptional EMI shielding, sensing, Joule heating, and antibacterial and shape memory properties. In short, this multifunctional intelligent composite material has great application prospects in flexible wearable electronics.
ABSTRACT
Candida albicans is a normal resident of humans and also a prevalent fungal pathogen. Lactate, a nonfermentative carbon source available in numerous anatomical niches, can be used by C. albicans as a carbon source. However, the key regulator(s) involved in this process remain unknown. Here, through a genetic screen, we report the identification of a transcription factor Zcf24 that is specifically required for lactate utilization in C. albicans. Zcf24 is responsible for the induction of CYB2, a gene encoding lactate dehydrogenase that is essential for lactate catabolism, in response to lactate. Chromatin immunoprecipitation showed a significantly higher signal of Zcf24 on the CYB2 promoter in lactate-grown cells than that in glucose-grown cells. Genome-wide transcription profiling indicates that, in addition to CYB2, Zcf24 regulates genes involved in the ß-oxidation of fatty acids, iron transport, and drug transport. Surprisingly, deleting ZCF24 confers enhanced commensal fitness. This could be attributed to Crz1-activated ß-glucan masking in the zcf24 mutant. The orthologs of Zcf24 are distributed in species most closely to C. albicans and some filamentous fungal species. Altogether, Zcf24 is the first transcription factor identified to date that regulates lactate catabolism in C. albicans and it is also involved in the regulation of commensalism.
Subject(s)
Candida albicans , Fungal Proteins , Lactic Acid , Transcription Factors , Candida albicans/metabolism , Carbon/metabolism , Fungal Proteins/genetics , Fungal Proteins/metabolism , Gene Expression Regulation, Fungal , Lactic Acid/metabolism , Symbiosis , Transcription Factors/genetics , Transcription Factors/metabolism , Zinc FingersABSTRACT
Candida albicans is an important opportunistic fungal pathogen of immunocompromised individuals. The ability to switch between yeast and hyphal growth forms is critical for its pathogenesis. Hyphal development in C. albicans requires two temporally linked regulations for initiation and maintenance. Here, we performed transcriptome sequencing (RNA-Seq) to analyze the transcriptional consequences for the two different phases of hyphal development. Genome-wide transcription profiling reveals that the sets associated with hyphal initiation were significantly enriched in genes for hyphal cell wall, biofilm matrix and actin polarization. In addition to hypha-specific genes, numerous genes involved in iron acquisition, such as FTR1 and SEF1, are highly induced specifically during sustained hyphal development even when additional free iron is supplied in the medium. Therefore, iron uptake genes are induced by signals that can support prolonged hyphal development in an iron-independent manner. The induction of iron acquisition genes during hyphal elongation was further confirmed by quantitative reverse transcription-PCR under various hypha-inducing conditions. Remarkably, preventing C. albicans from acquiring iron blocks BRG1 activation, leading to impaired hyphal maintenance, and ectopically expressed BRG1 can sustain hyphal development bypassing the requirement of iron. Our study elucidates an underlying mechanism of how multiple virulence factors are interconnected and are induced simultaneously during infection.
Subject(s)
Candida albicans/growth & development , Candida albicans/metabolism , Fungal Proteins/metabolism , Hyphae/growth & development , Iron/metabolism , Candida albicans/genetics , Fungal Proteins/genetics , Hyphae/genetics , Hyphae/metabolism , VirulenceABSTRACT
BACKGROUND: FAM98A, a novel protein, is expressed in ovarian and colorectal cancer tissues. However, the association between FAM98A expression and the clinicopathological characteristics of non-small cell lung cancer (NSCLC) remains undetermined. MATERIALS AND METHODS: The FAM98A expression pattern was determined in NSCLC samples and corresponding adjacent normal lung tissues using immunohistochemical staining and Western blotting. The association of FAM98A expression with clinicopathological characteristics was measured in 131 NSCLC samples. Finally, the overexpression and inhibition of FAM98A was performed in the A549 and SPC-A1 cell lines to explore its role in the development of lung cancer. RESULTS: Western blot analysis of 20 paired NSCLC samples showed that expression of FAM98A was higher in lung cancer tissues than in the corresponding adjacent normal lung tissues (p<0.05). Immunohistochemical staining of 128 NSCLC specimens showed that expression of FAM98A was significantly higher in lung cancer samples than in adjacent normal lung tissues (118/128 vs 10/128; p<0.001). Positive expression of FAM98A was significantly related to tumor TNM stage (p<0.05) and lymph node metastasis (p<0.001). Additionally, overexpression of FAM98A induced an increase in the expression of phosphorylated P38, phosphorylated ATF2, and cyclin D1, which promoted proliferation of lung cancer cells. Correspondingly, the effects of FAM98A overexpression were reversed by administration of a specific inhibitor of phosphorylated P38. CONCLUSION: FAM98A was overexpressed in the cytoplasm of NSCLC samples and correlated with advanced TNM staging and lymph node metastasis. Thus, FAM98A increases the expression of cyclin D1 by activating the P38-ATF2 signaling pathway and subsequently enhancing tumor cell proliferation; these results are promising and need further validation.