Osmotic Stress Influences Microtubule Drug Response Via WNK1 Kinase Signaling DOI
Ana Monfort‐Vengut, Natalia Sanz‐Gómez,

Sandra Ballesteros-Sánchez

et al.

Published: July 10, 2024

ABSTRACT Ion homeostasis is critical for numerous cellular processes, and disturbances in ionic balance underlie diverse pathological conditions, including cancer progression. Targeting ion even considered as a strategy to treat cancer. However, very little known about how may influence anticancer drug response. In genome-wide CRISPR-Cas9 resistance screen, we identified validated the master osmostress regulator WNK1 kinase modulator of response mitotic rigosertib. Osmotic stress inactivation lead an altered not only rigosertib treatment but also other microtubule-related drugs, minimizing prototypical arrest produced by these drugs. This effect due alteration microtubule stability polymerization dynamics, likely maintained fluctuations intracellular molecular crowding upon inactivation. promotes depolymerizing increased sensitivity stabilizing summary, our data proposes osmoregulation activity biomarker microtubule-associated chemotherapy

Language: Английский

Drosophila Model for Gut-Mediated Horizontal Transfer of Narrow- and Broad-Host-Range Plasmids DOI
Logan C. Ott,

Mark Engelken,

Sara M. Scott

et al.

mSphere, Journal Year: 2021, Volume and Issue: 6(5)

Published: Oct. 20, 2021

Horizontal gene transfer (HGT) is a driving force of microbial evolution. The gut animals acts as potent reservoir for the lateral virulence, fitness, and antimicrobial resistance genes through plasmids. Reduced-complexity models examination host-microbe interactions involved in plasmid are greatly desired. Thus, this study identifies use Drosophila melanogaster model organism conjugation plasmids various incompatibility groups gut. Enterobacteriaceae pairs were identified vitro used oral inoculation Flies enumerated donor, recipient, transconjugant populations. Each donor-recipient pair was observed to persist fly guts duration experiment. Gut concentrations donors recipients significantly different between male female flies, with females generally demonstrating increased concentrations. Furthermore, host genetics altered recipients. However, not affected by sex or detected only IncPε IncI1 groups. This demonstrates gut-mediated transfer. IMPORTANCE Microbial evolution due horizontal significant interest well within context human animal health. populations evolve host, factors from bacteria interact regulate little currently known about how bacterial plasmid-mediated HGT roles sexual dimorphism

Language: Английский

Citations

7

Drosophila suzukii displays a sex-dependent immune response to Microbacterium thalassium and Providencia sp. infection DOI
Rodrigo Bravin Narciso, Sara Sario, Rafael J. Mendes

et al.

Biological Control, Journal Year: 2023, Volume and Issue: 181, P. 105204 - 105204

Published: March 6, 2023

Language: Английский

Citations

2

Enteric bacterial infection in Drosophila induces whole-body alterations in metabolic gene expression independently of the immune deficiency signaling pathway DOI Creative Commons

Rujuta Deshpande,

Byoungchun Lee, Savraj Grewal

et al.

G3 Genes Genomes Genetics, Journal Year: 2022, Volume and Issue: 12(11)

Published: July 4, 2022

Abstract When infected by intestinal pathogenic bacteria, animals initiate both local and systemic defence responses. These responses are required to reduce pathogen burden also alter host physiology behavior promote infection tolerance, they often mediated through alterations in gene expression. Here, we have used transcriptome profiling examine expression changes induced enteric with the Gram-negative bacteria Pseudomonas entomophila adult female Drosophila. We find that induces a strong upregulation of metabolic expression, including gut fat body-enriched genes involved lipid transport, lipolysis, beta-oxidation, as well glucose amino acid metabolism genes. Furthermore, classic innate immune deficiency (Imd)/Relish/NF-KappaB pathway is not for, some cases limits, these infection-mediated increases see downregulates many transcription factors cell–cell signaling molecules, particularly those previously shown be gut-to-brain neuronal signaling. Moreover, genes, occurred largely independent Imd pathway. Together, our study identifies metabolic, signaling, factor may contribute organismal physiological behavioral infection.

Language: Английский

Citations

3

Sex-specific deubiquitylation drives immune-related neurodegeneration inDrosophila DOI Creative Commons

Jingnu Xia,

Adán Pinto-Fernández, Andreas Damianou

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2022, Volume and Issue: unknown

Published: Dec. 11, 2022

Summary Risk of neurodegenerative disease such as late onset Alzheimer’s is linked to aberrant ubiquitinylation and accumulation non-degraded proteins in brain cells. A glial network innate immune genes modulates inflammatory responses protein deposition. However, vulnerability differs between the sexes. Here, we show that Drosophila homologue deubiquitylase Trabid can align sex-specific aspects phenotypes with changes ubiquitylation activity. An enzymatically null flies, caused locomotion, sleep patterns, histology ultimately, lifespan. These were underscored by altered ubiquitin proteome enrichment profiles same enzymatic activity its human counterpart. When sex-determination gene transformer was silenced astrocytes or immunocompetent tissues, sex differences significantly reduced. Our results indicate underscores sex-specificity neurology, controlling balance inflammation.

Language: Английский

Citations

3

Osmotic Stress Influences Microtubule Drug Response Via WNK1 Kinase Signaling DOI
Ana Monfort‐Vengut, Natalia Sanz‐Gómez,

Sandra Ballesteros-Sánchez

et al.

Published: July 10, 2024

ABSTRACT Ion homeostasis is critical for numerous cellular processes, and disturbances in ionic balance underlie diverse pathological conditions, including cancer progression. Targeting ion even considered as a strategy to treat cancer. However, very little known about how may influence anticancer drug response. In genome-wide CRISPR-Cas9 resistance screen, we identified validated the master osmostress regulator WNK1 kinase modulator of response mitotic rigosertib. Osmotic stress inactivation lead an altered not only rigosertib treatment but also other microtubule-related drugs, minimizing prototypical arrest produced by these drugs. This effect due alteration microtubule stability polymerization dynamics, likely maintained fluctuations intracellular molecular crowding upon inactivation. promotes depolymerizing increased sensitivity stabilizing summary, our data proposes osmoregulation activity biomarker microtubule-associated chemotherapy

Language: Английский

Citations

0