Face/Off: The Interchangeable Side of Candida Albicans

Due to limited mobility, fungi, like most unicellular organisms, have evolved mechanisms to adapt to sudden chemical and/or physical variation in their environment. Candida albicans is recognized as a model organism to study eukaryotic responses to environmental changes, as this human commensal yeast but also opportunistic pathogen responds to numerous environmental cues through switching morphologies from yeast to hyphae growth. This mechanism is largely controlled by two major pathways: cAMP-PKA and MAPK, but each environmental signal is sensed by specific sensors. However, morphological switching is not the only response C. albicans exerts in response to environmental cues. Recently, fungal cell wall remodeling in response to host-derived environmental cues has been identified as a way for C. albicans to manipulate the innate immune system. The fungal cell wall is composed of a chitin skeleton linked to a network of β-glucan, which anchors proteins and mannans to the fungal cell surface. As localized on the cell surface, these molecules drive interactions with the environment and other cells, particularly with host immune cells. C. albicans is recognized by immune cells such as neutrophils and macrophages via pathogen recognition receptors (PRRs) that bind different components of the cell wall. While β-glucan and mannan are proinflammatory molecules, chitin can induce anti-inflammatory responses. Interestingly, C. albicans is able to regulate the exposure of these pathogen-associated molecular patterns (PAMPs) according to environmental cues resulting in a modulation of the host immune response. This review describes the mechanisms involved in C. albicans response to environmental changes and their effect on immune recognition

Communication in Fungi

We will discuss fungal communication in the context of fundamental biological functions including mating, growth, morphogenesis, and the regulation of fungal virulence determinants. We will address intraspecies but also interkingdom signaling by systematically discussing the sender of the message, the molecular message, and receiver. Analyzing communication shows the close coevolution of fungi with organisms present in their environment giving insights into multispecies communication. A better understanding of the molecular mechanisms underlying microbial communication will promote our understanding of the “fungal communicome.

Remasking of Candida albicans β-Glucan in Response to Environmental pH Is Regulated by Quorum Sensing

Candida albicans is a commensal yeast of the human gut which is tolerated by the immune system but has the potential to become an opportunistic pathogen. One way in which C. albicans achieves this duality is through concealing or exposing cell wall pathogen-associated molecular patterns (PAMPs) in response to host-derived environment cues (pH, hypoxia, and lactate). This cell wall remodeling allows C. albicans to evade or hyperactivate the host’s innate immune responses, leading to disease. Previously, we showed that adaptation of C. albicans to acidic environments, conditions encountered during colonization of the female reproductive tract, induces significant cell wall remodeling resulting in the exposure of two key fungal PAMPs (β-glucan and chitin). Here, we report that this pH-dependent cell wall remodeling is time dependent, with the initial change in pH driving cell wall unmasking, which is then remasked at later time points. Remasking of β-glucan was mediated via the cell density-dependent fungal quorum sensing molecule farnesol, while chitin remasking was mediated via a small, heat-stable, nonproteinaceous secreted molecule(s). Transcript profiling identified a core set of 42 genes significantly regulated by pH over time and identified the transcription factor Efg1 as a regulator of chitin exposure through regulation of CHT2. This dynamic cell wall remodeling influenced innate immune recognition of C. albicans, suggesting that during infection, C. albicans can manipulate the host innate immune responses

Violent conflict exacerbated drought-related food insecurity between 2009 and 2019 in sub-Saharan Africa

Conflict, drought and locusts are leading concerns for African food security but the relative importance and spatiotemporal scale of crises resulting from each hazard is poorly characterized. Here we use continuous, subnational data to demonstrate that the rise of food insecurity across sub-Saharan Africa that began in 2014 is attributable to an increase in violent conflict, particu- larly in South Sudan and Nigeria. Although drought remains a leading trigger of food crises, the prevalence of drought-related crises did not increase from 2009 to 2018. When exposed to drought, pastoralists experienced more widespread, severe and long-lasting food crises than people living in agricultural zones. Food insecurity remained elevated in pastoral regions for 2 years following a drought, while agricultural regions returned to pre-drought food-security levels in ~12 months. The few con- firmed famines during the 2009–2018 period coincided with both conflict and drought, while locusts had little effect on food security during this period

Microbial exposure during early human development primes fetal immune cells

Human fetal immune system begins to develop early during gestation, however factors responsible for fetal immune-priming remain elusive. We explored potential exposure to microbial agents in-utero and their contribution towards activation of memory T cells in fetal tissues. We profiled microbes across fetal organs using 16S-rRNA gene sequencing and detected low but consistent microbial signal in fetal gut, skin, placenta and lungs, in 2nd trimester of gestation. We identified several live bacterial strains including Staphylococcus and Lactobacillus in fetal tissues, which induced in vitro activation of memory T cells in fetal mesenteric lymph-node, supporting the role of microbial exposure in fetal immune-priming. Finally, using SEM and RNA-ISH, we visualised discrete localisation of bacteria-like structures and eubacterial-RNA within 14th week fetal gut lumen. These findings indicate selective presence of live-microbes in fetal organs during 2nd trimester of gestation and have broader implications towards establishment of immune competency and priming before birt

The bZIP Transcription Factor Rca1p Is a Central Regulator of a Novel CO2 Sensing Pathway in Yeast

Like many organisms the fungal pathogen Candida albicans senses changes in the environmental CO2 concentration. This response involves two major proteins: adenylyl cyclase and carbonic anhydrase (CA). Here, we demonstrate that CA expression is tightly controlled by the availability of CO2 and identify the bZIP transcription factor Rca1p as the first CO2 regulator of CA expression in yeast. We show that Rca1p upregulates CA expression during contact with mammalian phagocytes and demonstrate that serine 124 is critical for Rca1p signaling, which occurs independently of adenylyl cyclase. ChIP-chip analysis and the identification of Rca1p orthologs in the model yeast Saccharomyces cerevisiae (Cst6p) point to the broad significance of this novel pathway in fungi. By using advanced microscopy we visualize for the first time the impact of CO2 build-up on gene expression in entire fungal populations with an exceptional level of detail. Our results present the bZIP protein Rca1p as the first fungal regulator of carbonic anhydrase, and reveal the existence of an adenylyl cyclase independent CO2 sensing pathway in yeast. Rca1p appears to regulate cellular metabolism in response to CO2 availability in environments as diverse as the phagosome, yeast communities or liquid culture

Msb2 Shedding Protects Candida albicans against Antimicrobial Peptides

Msb2 is a sensor protein in the plasma membrane of fungi. In the human fungal pathogen C. albicans Msb2 signals via the Cek1 MAP kinase pathway to maintain cell wall integrity and allow filamentous growth. Msb2 doubly epitope-tagged in its large extracellular and small cytoplasmic domain was efficiently cleaved during liquid and surface growth and the extracellular domain was almost quantitatively released into the growth medium. Msb2 cleavage was independent of proteases Sap9, Sap10 and Kex2. Secreted Msb2 was highly O-glycosylated by protein mannosyltransferases including Pmt1 resulting in an apparent molecular mass of >400 kDa. Deletion analyses revealed that the transmembrane region is required for Msb2 function, while the large N-terminal and the small cytoplasmic region function to downregulate Msb2 signaling or, respectively, allow its induction by tunicamycin. Purified extracellular Msb2 domain protected fungal and bacterial cells effectively from antimicrobial peptides (AMPs) histatin-5 and LL-37. AMP inactivation was not due to degradation but depended on the quantity and length of the Msb2 glycofragment. C. albicans msb2 mutants were supersensitive to LL-37 but not histatin-5, suggesting that secreted rather than cell-associated Msb2 determines AMP protection. Thus, in addition to its sensor function Msb2 has a second activity because shedding of its glycofragment generates AMP quorum resistance

A climate of exclusion? Environmental migration, political marginalization and violence

Despite alarmist claims in the public discourse about the consequences of environmentally-induced migration for security, little empirical research has attempted to evaluate the contention. This dissertation, therefore, sets out to examine the linkage between environmental change, rural-urban migration, and nativist violence. To do so, it presents new data on rural-urban migration for 17 Sub-Saharan African countries. The findings unambiguously indicate that climate change does affect rural-urban migration flows, but only to a limited extent. In turn, these migratory flows may cause a moderate increase in the probability of nativist violence, particularly when the native population is marginalized by the central government. The findings, thus, reject the alarmist predictions. Climate change is unlikely to cause mass migration and, as a consequence, to substantially destabilize states

Communication in Fungi

We will discuss fungal communication in the context of fundamental biological functions including mating, growth, morphogenesis, and the regulation of fungal virulence determinants. We will address intraspecies but also interkingdom signaling by systematically discussing the sender of the message, the molecular message, and receiver. Analyzing communication shows the close coevolution of fungi with organisms present in their environment giving insights into multispecies communication. A better understanding of the molecular mechanisms underlying microbial communication will promote our understanding of the "fungal communicome.&quot