Transcriptomic profiling in childhood H1N1/09 influenza reveals reduced expression of protein synthesis genes.

We compared the blood RNA transcriptome of children hospitalized with influenza A H1N1/09, respiratory syncytial virus (RSV) or bacterial infection, and healthy controls. Compared to controls, H1N1/09 patients showed increased expression of inflammatory pathway genes and reduced expression of adaptive immune pathway genes. This was validated on an independent cohort.

Glutathione and Gts1p drive beneficial variability in the cadmium resistances of individual yeast cells.

Phenotypic heterogeneity among individual cells within isogenic populations is widely documented, but its consequences are not well understood. Here, cell-to-cell variation in the stress resistance of Saccharomyces cerevisiae, particularly to cadmium, was revealed to depend on the antioxidant glutathione. Heterogeneity was decreased strikingly in gsh1 mutants.

Phenotypic heterogeneity can enhance rare-cell survival in 'stress-sensitive' yeast populations.

Individual cells within isogenic microbial cultures exhibit phenotypic heterogeneity, an issue that is attracting intense interest. Heterogeneity could confer benefits, in generating variant subpopulations that may be better equipped to persist during perturbation. We tested this hypothesis by comparing the survival of wild-type Saccharomyces cerevisiae with that of mutants which are considered stress-sensitive but which, we demonstrate, also have increased heterogeneity.

Oxidative protein damage causes chromium toxicity in yeast.

Oxidative damage in microbial cells occurs during exposure to the toxic metal chromium, but it is not certain whether such oxidation accounts for the toxicity of Cr. Here, a Saccharomyces cerevisiae sod1Delta mutant (defective for the Cu,Zn-superoxide dismutase) was found to be hypersensitive to Cr(VI) toxicity under aerobic conditions, but this phenotype was suppressed under anaerobic conditions. Studies with cells expressing a Sod1p variant (Sod1(H46C)) showed that the superoxide dismutase activity rather than the metal-binding function of Sod1p was required for Cr resistance.

Iron blocks the accumulation and activity of tetracyclines in bacteria.

The apparent sensitivities of several bacterial pathogens to tetracyclines varied by up to 128-fold with the medium content of Fe, but not of other metals. The effect of Fe was independent of superoxide dismutase activity and of intracellular Fe, but accumulation of tetracyclines was blocked in high-Fe medium. Thus, synergistic suppression of bacterial growth in the presence of a low Fe concentration and tetracyclines arises because of elevated antibiotic accumulation.

Cell cycle- and age-dependent activation of Sod1p drives the formation of stress resistant cell subpopulations within clonal yeast cultures.

Phenotypic heterogeneity describes non-genetic variation that exists between individual cells within isogenic populations. The basis for such heterogeneity is not well understood, but it is evident in a wide range of cellular functions and phenotypes and may be fundamental to the fitness of microorganisms. Here we use a suite of novel assays applied to yeast, to provide an explanation for the classic example of heterogeneous resistance to stress (copper).