Interactions of Both Pathogenic and Nonpathogenic CUG Clade Candida Species with Macrophages Share a Conserved Transcriptional Landscape.

Candida species are a leading cause of opportunistic, hospital-associated bloodstream infections with high mortality rates, typically in immunocompromised patients. Several species, including Candida albicans, the most prevalent cause of infection, belong to the monophyletic CUG clade of yeasts. Innate immune cells such as macrophages are crucial for controlling infection, and C. albicans responds to phagocytosis by a coordinated induction of pathways involved in catabolism of nonglucose carbon sources, termed alternative carbon metabolism, which together are essential for virulence. However, the interactions of other CUG clade species with macrophages have not been characterized. Here, we analyzed transcriptional responses to macrophage phagocytosis by six Candida species across a range of virulence and clinical importance. We define a core induced response common to pathogenic and nonpathogenic species alike, heavily weighted to alternative carbon metabolism. One prominent pathogen, Candida parapsilosis, showed species-specific expansion of phagocytosis-responsive genes, particularly metabolite transporters. C. albicans and Candida tropicalis, the other prominent pathogens, also had species-specific responses, but these were largely comprised of functionally uncharacterized genes. Transcriptional analysis of macrophages also demonstrated highly correlated proinflammatory transcriptional responses to different Candida species that were largely independent of fungal viability, suggesting that this response is driven by recognition of conserved cell wall components. This study significantly broadens our understanding of host interactions in CUG clade species, demonstrating that although metabolic plasticity is crucial for virulence in Candida, it alone is not sufficient to confer pathogenicity. Instead, we identify sets of mostly uncharacterized genes that may explain the evolution of pathogenicity. IMPORTANCE Candidiasis is a major fungal infection by Candida species, causing life-threatening invasive disease in immunocompromised patients. C. albicans, which is adapted to commensalism of human mucosae, is the most common cause. While several other species cause infection, most are less prevalent or less virulent. As innate immune cells are the primary defense against Candida infection, we compared the transcriptional responses of C. albicans and related species to phagocytosis by macrophages, to understand the basis of variation in pathogenesis. This response, including the metabolic remodeling required for virulence in C. albicans, was strikingly conserved across the virulence spectrum. Macrophage responses to different species were also highly similar. This study indicates that important elements of host-pathogen interactions in C. albicans are not driven by adaptation to the mammalian host and improves our understanding of pathogenicity in opportunistic fungal species that are understudied but collectively impose a significant threat of their own.

Radar sounding of the Medusae Fossae Formation Mars: equatorial ice or dry, low-density deposits?

The equatorial Medusae Fossae Formation (MFF) is enigmatic and perhaps among the youngest geologic deposits on Mars. They are thought to be composed of volcanic ash, eolian sediments, or an ice-rich material analogous to polar layered deposits. The Mars Advanced Radar for Subsurface and Ionospheric Sounding (MARSIS) instrument aboard the Mars Express Spacecraft has detected nadir echoes offset in time-delay from the surface return in orbits over MFF material. These echoes are interpreted to be from the subsurface interface between the MFF material and the underlying terrain. The delay time between the MFF surface and subsurface echoes is consistent with massive deposits emplaced on generally planar lowlands materials with a real dielectric constant of approximately 2.9 +/- 0.4. The real dielectric constant and the estimated dielectric losses are consistent with a substantial component of water ice. However, an anomalously low-density, ice-poor material cannot be ruled out. If ice-rich, the MFF must have a higher percentage of dust and sand than polar layered deposits. The volume of water in an ice-rich MFF deposit would be comparable to that of the south polar layered deposits.

Subsurface radar sounding of the south polar layered deposits of Mars.

The ice-rich south polar layered deposits of Mars were probed with the Mars Advanced Radar for Subsurface and Ionospheric Sounding on the Mars Express orbiter. The radar signals penetrate deep into the deposits (more than 3.7 kilometers). For most of the area, a reflection is detected at a time delay that is consistent with an interface between the deposits and the substrate. The reflected power from this interface indicates minimal attenuation of the signal, suggesting a composition of nearly pure water ice. Maps were generated of the topography of the basal interface and the thickness of the layered deposits. A set of buried depressions is seen within 300 kilometers of the pole. The thickness map shows an asymmetric distribution of the deposits and regions of anomalous thickness. The total volume is estimated to be 1.6 x 10(6) cubic kilometers, which is equivalent to a global water layer approximately 11 meters thick.

MARSIS radar sounder evidence of buried basins in the northern lowlands of Mars.

A hemispheric dichotomy on Mars is marked by the sharp contrast between the sparsely cratered northern lowland plains and the heavily cratered southern highlands. Mechanisms proposed to remove ancient crust or form younger lowland crust include one or more giant impacts, subcrustal transport by mantle convection, the generation of thinner crust by plate tectonics, and mantle overturn following solidification of an early magma ocean. The age of the northern lowland crust is a significant constraint on these models. The Mars Advanced Radar for Subsurface and Ionospheric Sounding (MARSIS) instrument on the European Space Agency's Mars Express spacecraft is providing new constraints on the martian subsurface. Here we show evidence of buried impact basins ranging in diameter from about 130 km to 470 km found over approximately 14 per cent of the northern lowlands. The number of detected buried basins >200 km in diameter indicates that the lowland crust is ancient, dating back to the Early Noachian epoch. This crater density is a lower limit because of the likelihood that not all buried basins in the area surveyed by MARSIS have been detected. An Early Noachian age for the lowland crust has been previously suggested on the basis of a large number of quasi-circular topographic depressions interpreted to be evidence of buried basins. Only a few of these depressions in the area surveyed by MARSIS, however, correlate with the detected subsurface echoes. On the basis of the MARSIS data, we conclude that the northern lowland crust is at least as old as the oldest exposed highland crust. This suggests that the crustal dichotomy formed early in the geologic evolution of Mars.

Oxidant enhancement in martian dust devils and storms: implications for life and habitability.

We investigate a new mechanism for producing oxidants, especially hydrogen peroxide (H2O2), on Mars. Large-scale electrostatic fields generated by charged sand and dust in the martian dust devils and storms, as well as during normal saltation, can induce chemical changes near and above the surface of Mars. The most dramatic effect is found in the production of H2O2 whose atmospheric abundance in the "vapor" phase can exceed 200 times that produced by photochemistry alone. With large electric fields, H2O2 abundance gets large enough for condensation to occur, followed by precipitation out of the atmosphere. Large quantities of H2O2 would then be adsorbed into the regolith, either as solid H2O2 "dust" or as re-evaporated vapor if the solid does not survive as it diffuses from its production region close to the surface. We suggest that this H2O2, or another superoxide processed from it in the surface, may be responsible for scavenging organic material from Mars. The presence of H2O2 in the surface could also accelerate the loss of methane from the atmosphere, thus requiring a larger source for maintaining a steady-state abundance of methane on Mars. The surface oxidants, together with storm electric fields and the harmful ultraviolet radiation that readily passes through the thin martian atmosphere, are likely to render the surface of Mars inhospitable to life as we know it.

Oxidant enhancement in martian dust devils and storms: storm electric fields and electron dissociative attachment.

Laboratory studies, numerical simulations, and desert field tests indicate that aeolian dust transport can generate atmospheric electricity via contact electrification or "triboelectricity." In convective structures such as dust devils and dust storms, grain stratification leads to macroscopic charge separations and gives rise to an overall electric dipole moment in the aeolian feature, similar in nature to the dipolar electric field generated in terrestrial thunderstorms. Previous numerical simulations indicate that these storm electric fields on Mars can approach the ambient breakdown field strength of approximately 25 kV/m. In terrestrial dust phenomena, potentials ranging from approximately 20 to 160 kV/m have been directly measured. The large electrostatic fields predicted in martian dust devils and storms can energize electrons in the low pressure martian atmosphere to values exceeding the electron dissociative attachment energy of both CO2 and H2O, which results in the formation of the new chemical products CO/O- and OH/H-, respectively. Using a collisional plasma physics model, we present calculations of the CO/O- and OH/H- reaction and production rates. We demonstrate that these rates vary geometrically with the ambient electric field, with substantial production of dissociative products when fields approach the breakdown value of approximately 25 kV/m. The dissociation of H2O into OH/H- provides a key ingredient for the generation of oxidants; thus electrically charged dust may significantly impact the habitability of Mars.

Radar soundings of the subsurface of Mars.

The martian subsurface has been probed to kilometer depths by the Mars Advanced Radar for Subsurface and Ionospheric Sounding instrument aboard the Mars Express orbiter. Signals penetrate the polar layered deposits, probably imaging the base of the deposits. Data from the northern lowlands of Chryse Planitia have revealed a shallowly buried quasi-circular structure about 250 kilometers in diameter that is interpreted to be an impact basin. In addition, a planar reflector associated with the basin structure may indicate the presence of a low-loss deposit that is more than 1 kilometer thick.