FANCD2 modulates the mitochondrial stress response to prevent common fragile site instability.

Common fragile sites (CFSs) are genomic regions frequently involved in cancer-associated rearrangements. Most CFSs lie within large genes, and their instability involves transcription- and replication-dependent mechanisms. Here, we uncover a role for the mitochondrial stress response pathway in the regulation of CFS stability in human cells.

Assessing the consequences of environmental exposures on the expression of the human receptor and proteases involved in SARS-CoV-2 cell-entry.

The role of environmental condition on the infection by the novel pathogenic SARS-CoV-2 virus remains uncertain. In here, exploiting a large panel of publicly available genome-wide data, we investigated whether the human receptor ACE2 and human proteases TMPRSS2, FURIN and CATHEPSINs (B, L and V), which are involved in SARS-CoV-2 cell entry, are transcriptionally regulated by environmental cues. We report that more than 50 chemicals modulate the expression of ACE2 or human proteases important for SARS-CoV-2 cell entry.

Depletion of ZBTB38 potentiates the effects of DNA demethylating agents in cancer cells via CDKN1C mRNA up-regulation.

DNA methyltransferase inhibitor (DNMTi) treatments have been used for patients with myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML), and have shown promising beneficial effects in some other types of cancers. Here, we demonstrate that the transcriptional repressor ZBTB38 is a critical regulator of the cellular response to DNMTi. Treatments with 5-azacytidine, or its derivatives decitabine and zebularine, lead to down-regulation of ZBTB38 protein expression in cancer cells, in parallel with cellular damage.

Strong increase in the autofluorescence of cells signals struggle for survival.

Prokaryotic and eukaryotic cells exhibit an intrinsic natural fluorescence due to the presence of fluorescent cellular structural components and metabolites. Therefore, cellular autofluorescence (AF) is expected to vary with the metabolic states of cells. We examined how exposure to the different stressors changes the AF of Escherichia coli cells.

Antibiotic Susceptibility Testing of the Gram-Negative Bacteria Based on Flow Cytometry.

Rapidly treating infections with adequate antibiotics is of major importance. This requires a fast and accurate determination of the antibiotic susceptibility of bacterial pathogens. The most frequently used methods are slow because they are based on the measurement of growth inhibition.

Massive diversification in aging colonies of Escherichia coli.

The evolutionary success of bacteria depends greatly on their capacity to continually generate phenotypic diversity. Structured environments are particularly favorable for diversification because of attenuated clonal interference, which renders selective sweeps nearly impossible and enhances opportunities for adaptive radiation. We examined at the microscale level the emergence and the spatial and temporal dynamics of phenotypic diversity and their underlying causes in Escherichia coli colonies.

Molecular and evolutionary bases of within-patient genotypic and phenotypic diversity in Escherichia coli extraintestinal infections.

Although polymicrobial infections, caused by combinations of viruses, bacteria, fungi and parasites, are being recognised with increasing frequency, little is known about the occurrence of within-species diversity in bacterial infections and the molecular and evolutionary bases of this diversity. We used multiple approaches to study the genomic and phenotypic diversity among 226 Escherichia coli isolates from deep and closed visceral infections occurring in 19 patients. We observed genomic variability among isolates from the same site within 11 patients.

Reliable detection of dead microbial cells by using fluorescent hydrazides.

We have developed a new method for accurate quantification of dead microbial cells. This technique employs the simultaneous use of fluorescent hydrazides and nucleic acid dyes. Fluorescent hydrazides allow detection of cells that cannot be detected with currently used high-affinity nucleic acid dyes.

Organised genome dynamics in the Escherichia coli species results in highly diverse adaptive paths.

The Escherichia coli species represents one of the best-studied model organisms, but also encompasses a variety of commensal and pathogenic strains that diversify by high rates of genetic change. We uniformly (re-) annotated the genomes of 20 commensal and pathogenic E. coli strains and one strain of E.

Causes and consequences of DNA repair activity modulation during stationary phase in Escherichia coli.

Escherichia coli responds to nutrient exhaustion by entering a state commonly referred to as the stationary phase. Cells entering the stationary phase redirect metabolic circuits to scavenge any available nutrients and become resistant to different stresses. However, many DNA repair pathways are downregulated in stationary-phase cells, which results in increased mutation rates.

Environmental tuning of mutation rates.

Through their life cycles, bacteria experience many different environments in which the relationship between available energy resources and the frequency and the nature of various stresses is highly variable. In order to survive in such changeable environments, bacteria must balance the need for nutritional competence with stress resistance. In Escherichia coli natural populations, this is most frequently achieved by changing the regulation of the RpoS sigma factor-dependent general stress response.

Stress and survival of aging Escherichia coli rpoS colonies.

In Escherichia coli, the expression of the RpoS regulon is known to be crucial for survival in liquid cultures during stationary phase. By measuring cell viability and by transcriptome analysis, here we show that rpoS cells as well as wild-type cells survive when they form colonies on solid media.