Interactions between colonizing commensal microorganisms and their hosts play important roles in health and disease. The opportunistic fungal pathogen Candida albicans is a common component of human intestinal flora. To gain insight into C. albicans colonization, genes expressed by fungi grown within a host were studied. The EFH1 gene, encoding a putative transcription factor, was highly expressed during growth of C. albicans in the intestinal tract. Counterintuitively, an efh1 null mutant exhibited increased colonization of the murine intestinal tract, a model of commensal colonization, whereas an EFH1 overexpressing strain exhibited reduced colonization of the intestinal tract and of the oral cavity of athymic mice, the latter situation modeling human mucosal candidiasis. When inoculated into the bloodstream of mice, both efh1 null and EFH1 overexpressing strains caused lethal infections. In contrast, other mutants are attenuated in virulence following intravenous inoculation but exhibited normal levels of intestinal colonization. Finally, although expression of several genes is dependent on transcription factor Efg1p during laboratory growth, Efg1p-independent expression of these genes was observed during growth within the murine intestinal tract. These results show that expression of EFH1 regulated the level of colonizing fungi, favoring commensalism as opposed to candidiasis. Also, different genes are required in different host niches and the pathway(s) that regulates gene expression during host colonization can differ from well-characterized pathways used during laboratory growth. Although the fungus Candida albicans commonly colonizes the human gastrointestinal tract as a commensal, the organism is also an opportunistic pathogen, responsible for a wide range of infections in immunocompromised persons. While numerous studies of infection have been conducted, few studies have analyzed the commensal state. The studies described here analyze C. albicans cells colonizing the intestinal tract of immunocompetent mice in the absence of disease, a model for commensalism. Results showed that expression of the putative transcription factor Efh1p by cells colonizing the intestinal tract was relatively high, but paradoxically, expression of Efh1p was associated with lower colonization. Efh1p had no detectable effect on the ability of C. albicans to cause lethal disseminated infection in mice. In contrast, Rbt1p and Rbt4p, two proteins of poorly defined function required for normal disseminated infection, were not required for intestinal colonization. These results argue that the commensal state is distinct from the pathogenic state and that different factors are important in different states. Also, the regulation of expression of genes RBT1, RBT4, and ECE1 during intestinal colonization differed from their well-characterized regulation during laboratory growth. Further studies of commensal colonization are needed to understand this important stage of C. albicans biology.

Emerging and low-carbon technologies and innovations are driving a need for domestic sources, sustainable use, and availability of critical minerals (CMs)—those vital to the national and economic security of the United States. Understanding the known and potential health effects of exposures to such mineral commodities can inform prudent and environmentally responsible handling and harvesting. We review the occurrence, use, predominant exposure pathways, and adverse outcome pathways (AOP) for human and fish receptors of those CMs that are nutritionally essential trace metals (specifically, cobalt, chromium, manganese, nickel, and zinc), as well as the rare earth elements. Biological responses to some elements having comparable biogeochemistry can sometimes be similar. Candidate quantifiable biomarkers for assessing potential AOP are conveyed.

Critical minerals (or critical elements) are minerals or elements that are essential to global security and development and have supply chains vulnerable to disruption. In general, knowledge of the environmental behavior and health effects of critical elements is needed to support the development of safe and environmentally responsible supplies. This knowledge includes identifying potential consequences of increased critical element production and use, alternative critical element sources such as mine wastes, and adverse effects of critical elements on ecosystem condition and organismal health. Here we identify significant data gaps in the understanding of critical elements in surficial and aquatic environments, and the need, given the large number of commodities (50) identified on the 2022 critical minerals list for the United States, for an approach to prioritize them for study of their environmental fate and effects. We propose a multidisciplinary approach for this prioritization, considering measures of occurrence, geochemistry, bioavailability, and toxicity. We describe relatively easy-to-obtain metrics for each of these topic areas and demonstrate the utility of this integrated prioritization approach using indium and zinc as examples. This approach facilitates prioritizing research with a focus on those critical elements that are most mobile in the environment, bioavailable, toxic, or simply lacking data in these categories.