Biology subjects

Gianetto, Q. G.

Publications and source records attributed to Gianetto, Q. G..

4 recordsLinked to original sources

bioRxiv2025

Nitrate-responsive Mycobacterial Intracytoplasmic Membranes dampen Inflammation during Mycobacterium tuberculosis Infection

Subcellular compartmentalization of metabolic processes is a main feature of prokaryotic and eukaryotic architecture. Environmental bacteria generate intracytoplasmic membranes (ICMs) as a crucial strategy to adapt their metabolism to environmental changes. While pathogenic intracellular bacteria also perceive various stressful stimuli during host interactions, the subsequent re-organization of their internal architecture has not been explored. Using cryo-electron tomography, we show that Mycobacterium tuberculosis (Mtb), a major human pathogen, is able to form ICMs outside and inside host cells in a strain-dependent manner. We characterize these Mycobacterial intracytoplasmic Membranes (MIMs) as nitrate-induced structures involved in regulation of metabolism. Furthermore, we uncover that MIM formation during macrophage infection correlates with the ability of Mtb to dampen cellular inflammatory responses. Our findings reveal a previously uncharacterized cytoplasmic structure in Mtb and link it to a functional mechanism that enables the bacterium to adapt to its intracellular niche.

microbiology↗

bioRxiv2025

Plasma protein biomarkers for the early detection of gastric preneoplasia and cancer: a prospective study

Gastric cancer (GC) often presents a poor prognosis due to its asymptomatic phenotype at early stages. Upper endoscopy, the current gold standard for diagnosis, is invasive with limited sensitivity for detecting gastric preneoplasia. Non-invasive biomarkers, such as blood circulating proteins offer a promising alternative for an early detection. Using mass spectrometry-based proteomics we identified plasma proteins as biomarkers of the presence of gastric preneoplasia and cancer lesions in an exploratory subgroup of patients (n=39). Fifteen promising protein candidates emerged to distinguish patient categories and were further confirmed by enzyme-linked immunosorbent assays (ELISA) in plasma samples from a cohort of 138 participants. Our predictive models demonstrated high classification performance with a minimal set of biomarkers, making them clinically applicable. Repeated cross-validations yielded high Area Under the Receiver Operating Characteristics (AUROC) values, notably distinguishing cancerous or precancerous cases from non-cancerous ones. Leveraging simple blood sampling, this strategy holds promise to detect high-risk gastric lesions, even at asymptomatic stages. Such an approach could significantly improve early detection and clinical management of GC, offering direct benefit for patients.

cancer biology↗

bioRxiv2024

Metabolic imprint of an intracellular pathogen drives histone hypermethylation and tunes the host transcriptional response to infection

Chlamydia trachomatis, an intracellular bacterium, highjacks metabolites from the host cell for its own proliferation. We provide evidence of global hypermethylation of the host proteome, including histones, during the late stages of infection. Single cell analyses revealed co-occurrence of several methylated residues on histones. Histone hypermethylation correlated with bacterial load and was prevented by antibiotic treatment. Mapping of trimethylation of histone 3 at residues K4 and K9 revealed a broad distribution throughout the chromatin. Nuclear fractions of infected cells exhibited a four-fold decrease of demethylase activity towards H3K4me3 and a two-fold increase in succinate concentration, a competitive inhibitor for the demethylase co-factor -ketoglutarate. Supplementation of the culture medium with dimethyl-ketoglutarate (DMKG) or with iron, a second co-factor of histone lysine demethylases, reduced histone hypermethylation. DMKG supplementation modified the transcription of about one third of the infection-responsive genes, indicating that histone hypermethylation contributes to modulating the transcriptional response of the host to infection. Finally, chemical inhibition of histone demethylases in a mouse model of infection showed a moderate benefit regarding the outcome of infection. Overall, our data show that the metabolic pressure exerted by a pathogen with an intracellular lifestyle drives epigenetic changes in infected cells.

cell biology↗

bioRxiv2022

Single locus phosphoproteomics reveals phosphorylation of RPA-1 is required for generation of single-strand DNA following a break at a subtelomeric locus.

Damage to the genetic material of the cell poses a universal threat to all forms of life. Central to the DNA damage response (DDR) is a phosphorylation signalling cascade that leads to the co-ordination of the cellular response to a DNA break. Identifying the proteins that are phosphorylated is crucial to understanding the mechanisms underlying this DDR. We have used SILAC-based quantitative phosphoproteomics to profile changes in phosphorylation site abundance following a single double strand break (DSB) at a chromosome internal locus and the subtelomeric bloodstream form expression site in Trypanosoma brucei. We report >6500 phosphorylation sites, including a core set of 211 DSB responsive phosphorylation sites. Along with phosphorylation of canonical DNA damage factors, we find that there is a striking distinction between the proteins phosphorylated in response to a chromosome internal DSB and one at the active BES and describe a single phosphorylation event on Replication factor A (RPA) 1 that is required for efficient resection at a bloodstream form expression site.

molecular biology↗