An Intersection between Iron Availability and Candida albicans Invasive Filamentation

Candida albicans filamentation, the ability to convert from oval yeast cells to elongated hyphal cells, is a key factor in its pathogenesis. Previous work has shown that the integral membrane protein Dfi1 is required for filamentation in cells grown in contact with a semi-solid surface. Investigations into the downstream targets of the Dfi1 pathway revealed potential links to two transcription factors – Sef1 and Czf1. Sef1 regulates iron uptake and iron utilization genes in low iron conditions, leading us to hypothesize that there exists a link between iron availability and contact-dependent invasive filamentation. Here, we showed that Sef1 was not required for contact dependent filamentation, but it was required for WT expression levels of a number of genes during growth in contact conditions. Czf1 is required for contact-dependent filamentation and for WT levels of expression of several genes. Constitutive expression and activation of either Sef1 or Czf1 individually in a dfi1 null strain resulted in a complete rescue of the dfi1 null filamentation defect. Because Sef1 is normally activated in low-iron environments, we embedded WT and dfi1 null cells in iron-free agar medium supplemented with various concentrations of Ferrous Ammonium Sulfate (FAS). dfi1 null cells embedded in media with a low concentration of iron (20uM FAS) showed increased filamentation in comparison to mutant cells embedded in higher concentrations of iron (50-500uM). WT cells produced filamentous colonies in all concentrations. Together, this data indicates that Dfi1, Czf1, Sef1, and environmental iron regulate C. albicans contact-dependent filamentation.

Excessive Reactive Iron Impairs Hematopoiesis by Affecting Both Immature Hematopoietic Cells and Stromal Cells

Iron overload is the accumulation of excess iron in the body that may occur as a result of various genetic disorders or as a consequence of repeated blood transfusions. The surplus iron is then stored in the liver, pancreas, heart and other organs, which may lead to chronic liver disease or cirrhosis, diabetes and heart disease, respectively. In addition, excessive iron may impair hematopoiesis, although the mechanisms of this deleterious effect is not entirely known. In this study, we found that ferrous ammonium sulfate (FeAS), induced growth arrest and apoptosis in immature hematopoietic cells, which was mediated via reactive oxygen species (ROS) activation of p38MAPK and JNK pathways. In in vitro hematopoiesis derived from embryonic stem cells (ES cells), FeAS enhanced the development of dysplastic erythroblasts but inhibited their terminal differentiation; in contrast, it had little effect on the development of granulocytes, megakaryocytes, and B lymphocytes. In addition to its directs effects on hematopoietic cells, iron overload altered the expression of several adhesion molecules on stromal cells and impaired the cytokine production profile of these cells. Therefore, excessive iron would affect whole hematopoiesis by inflicting vicious effects on both immature hematopoietic cells and stromal cells.

Mechanism of adsorption of cadmium and lead ions by iron-activated biochar

Heavy metal removal from aqueous matrices may help reduce disease and cancer incidences. In this study, reed biochar (RBC) and RBC modified by ferrous ammonium sulfate addition (1 mol Fe L-1) were compared for potential Cd and Pb removal from varying pH aqueous solutions. Surface functional groups were identified using Fourier transform infrared (FTIR) analysis, and their surface physicochemical structure was observed using scanning electron microscopy-energy dispersive spectrometry (SEM-EDS). Batch experiments showed that the modified-reed biochar (MRBC) had greater Cd and Pb removal capacities over a wide pH range (1 to 8), as well as greater metal sorption capacities compared to RBC. Metal reaction kinetics occurred relatively quickly (i.e., within 60 min), and Langmuir modeling suggested that Cd and Pb removal by MRBC was maximized at 2.97 mg g−1 and 17.5 mg g−1 at 45 °C, respectively. The MRBC effectively sorbed Cd and Pb likely due to associations with functional groups modified by the Fe addition. In the future, MRBC may be used as an efficient and eco-friendly adsorbent for Cd and Pb removal from aqueous solutions and may help reduce water-borne issues associated with metal contamination.

MODS-Wayne, a Colorimetric Adaptation of the Microscopic-Observation Drug Susceptibility (MODS) Assay for Detection ofMycobacterium tuberculosisPyrazinamide Resistance from Sputum Samples

ABSTRACTAlthough pyrazinamide (PZA) is a key component of first- and second-line tuberculosis treatment regimens, there is no gold standard to determine PZA resistance. Approximately 50% of multidrug-resistant tuberculosis (MDR-TB) and over 90% of extensively drug-resistant tuberculosis (XDR-TB) strains are also PZA resistant.pncAsequencing is the endorsed test to evaluate PZA susceptibility. However, molecular methods have limitations for their wide application. In this study, we standardized and evaluated a new method, MODS-Wayne, to determine PZA resistance. MODS-Wayne is based on the detection of pyrazinoic acid, the hydrolysis product of PZA, directly in the supernatant of sputum cultures by detecting a color change following the addition of 10% ferrous ammonium sulfate. Using a PZA concentration of 800 µg/ml, sensitivity and specificity were evaluated at three different periods of incubation (reading 1, reading 2, and reading 3) using a composite reference standard (MGIT-PZA,pncAsequencing, and the classic Wayne test). MODS-Wayne was able to detect PZA resistance, with a sensitivity and specificity of 92.7% and 99.3%, respectively, at reading 3. MODS-Wayne had an agreement of 93.8% and a kappa index of 0.79 compared to the classic Wayne test, an agreement of 95.3% and kappa index of 0.86 compared to MGIT-PZA, and an agreement of 96.9% and kappa index of 0.90 compared topncAsequencing. In conclusion, MODS-Wayne is a simple, fast, accurate, and inexpensive approach to detect PZA resistance, making this an attractive assay especially for low-resource countries, where TB is a major public health problem.