Biology subjects

Bloch, S.

Publications and source records attributed to Bloch, S..

5 recordsLinked to original sources

bioRxiv2026

Antibacterial activity of a newly identified phage-derived endolysin and its parental bacteriophage against clinical uropathogenic Escherichia coli

The increasing prevalence of antibiotic-resistant uropathogenic Escherichia coli highlights the need for antibacterial strategies that can complement or extend beyond conventional antibiotic treatment. Bacteriophages and phage-derived lytic enzymes represent promising alternatives because of their distinct mechanisms of bacterial killing and their potential activity against drug-resistant pathogens. In this study, we characterized the newly discovered UPEC-infecting bacteriophage vB-EcoS_57-3 and the endolysin 57_3Lys, encoded by this phage, combining genomic, structural, and functional approaches. The phage demonstrated lytic activity against clinical UPEC isolates and retained antibacterial potential under conditions relevant to the urinary tract. Genomic and sequence analyses revealed distinctive features of 57_3Lys associated with signal-anchor-release endolysins and suggested a less common mode of intracellular translocation and activation. Functional experiments supported the involvement of the bacterial secretion machinery in endolysin-mediated lysis. Notably, the purified enzyme also displayed antibacterial activity against intact clinical E. coli cells, despite the intrinsic barrier presented by the Gram-negative cell envelope. Although this activity developed slowly, it significantly reduced both bacterial culture turbidity and viable cell number. Together, these findings provide new insights into the antimicrobial strategies based on the phages and their phage lytic enzymes, supporting further exploration of vB-EcoS_57-3 and 57_3Lys as potential tools against antibiotic-resistant UPEC.

microbiology↗

bioRxiv2025

Disruption of emotional processing by GBR 12909 in male and female mice highlights novel behavioral paradigms relevant to bipolar disorders.

Bipolar disorders (BD) are defined by a chronic recurrence of manic and depressive phases. Along with mood, acute phases are associated with altered emotions. The biological underpinnings of these changes are unresolved, mostly because modeling the cycling nature of BD is still a major challenge in preclinical studies. One model is based on GBR 12909 administration, a dopamine transporter inhibitor aiming at mimicking some dimensions of mania. It has recently been shown that this model generates a mixed phenotype with negative hedonic biases and anxiety along with hyperlocomotion. These studies have been only performed in male animals, and other behavioral dimensions relevant for BD remain to be explored, in particular recognition of conspecifics emotions and reactivity to danger. The objective of this study is to further characterize the GBR model in both sexes by introducing two novel behavioral assays, the sweeping/looming disk and the negative emotion recognition tasks to evaluate response to threat and emotion discrimination. First, we replicated the previous results in the GBR model: higher anxiety, hyperlocomotion, anhedonia in males. These phenotypes were less pronounced in females. GBR also induced a hypersensibility to threat in both sexes in the sweeping/looming disk. GBR abolished preference for the emotional target only in males, suggesting altered emotion recognition. This work introduces new phenotypic dimensions relevant to study BD and highlights the necessity to study both sexes which are not strictly equivalent in their behavioral responses.

neuroscience↗

bioRxiv2023

NMR structure of the Orf63 pro-lytic protein from lambda bacteriophage

The orf63 gene resides in a region of the lambda bacteriophage genome between the exo and xis genes and is among the earliest genes transcribed during infection. In lambda phage and Shiga toxin (Stx) producing phages found in enterohemorrhagic E. coli (EHEC) associated with food poisoning, Orf63 expression reduces the host survival and hastens the period between infection and lysis thereby giving it pro-lysogenic qualities. The NMR structure of dimeric Orf63 reveals a fold consisting of two helices and one strand that all make extensive intermolecular contacts. Structure-based data mining failed to identify any Orf63 homolog beyond the family of temperate bacteriophages. A machine learning approach was used to design an amphipathic helical ligand that bound a hydrophobic cleft on Orf63. This approach may open a new path towards designing therapeutics that antagonize the contributions of Stx phages in EHEC outbreaks.

biochemistry↗

bioRxiv2021

Divergent sex differences in functional brain connectivity networks in excessively drinking C57BL/6J mice

Individuals with alcohol use disorder continue to drink in excess despite the health and societal consequences, and the rate of problematic drinking and alcohol-related harms is increased in women. Clinical imaging studies report widespread adaptations in brain structure after chronic, heavy drinking, and alcohol-related cues enhance brain reactivity in reward-related regions. In rodents, alcohol drinking induces expression of the immediate early gene c-Fos, which can be a marker of cellular activity, across multiple brain regions. Recent evidence also suggests that abstinence from chronic intermittent alcohol exposure can produce mesoscale changes in c-Fos expression. However, there is a substantial gap in our understanding of how excessive drinking affects functional connectivity networks to influence alcohol-seeking behaviors. For this study, male and female C57BL/6J mice were given access to either water or a choice between water and ethanol in the intermittent access drinking model for 4 weeks. After a short-access drinking session, whole brains from high alcohol drinking male and female mice and water drinking controls were then subjected to c-Fos immunolabeling, iDISCO+ clearing, light sheet imaging, and whole-brain c-Fos mapping. Correlation matrices were then generated and graph theoretical statistical approaches were used to determine changes in functional connectivity across sex and drinking condition. We observed robust sex differences in the network of c-Fos+ cells in water drinking mice, and excessive alcohol drinking produce divergent and robust changes in functional network connectivity in male and female mice. In addition, these analyses identified novel hub regions in excessively drinking mice that were unique for each sex. In conclusion, the whole-brain c-Fos mapping analysis identified sex difference in functional network connectivity and unique and understudied regions that may play a critical role in controlling excessive ethanol drinking in male and female mice.

neuroscience↗

bioRxiv2020

Non-thalamic origin of zebrafish sensory relay nucleus: convergent evolution of visual pathways in amniotes and teleosts

Ascending visual projections similar to the mammalian thalamocortical pathway are found in a wide range of vertebrate species, but their homologous relationship is debated. To get better insights into their evolutionary origin, we examined the developmental origin of a visual relay nucleus in zebrafish (a teleost fish). Similarly to the tectofugal visual thalamic nuclei in amniotes, the lateral part of the preglomerular complex (PG) in teleosts receives tectal information and projects to the pallium. However, our cell lineage study reveals that the majority of PG cells are derived from the midbrain, not from the forebrain. We also demonstrate that the PG projection neurons develop gradually until juvenile stage, unlike the thalamic projection neurons. Our data suggest that teleost PG is not homologous to the amniote thalamus and that thalamocortical-like projections can evolve from a non-forebrain cell population. Thus, sensory pathways in vertebrate brains exhibit a surprising degree of variation.

neuroscience↗