Biology subjects

Ayaydin, F.

Publications and source records attributed to Ayaydin, F..

3 recordsLinked to original sources

bioRxiv2026

A preclinical resistance framework discovers the virulence risks of antibiotics in development

Several new antibiotics target multidrug-resistant pathogens, yet resistance is still evaluated mainly by drug-susceptibility, leaving consequences for bacterial pathogenicity poorly understood. Here, we develop a framework integrating resistance evolution, genomic surveillance and host-pathogen phenotyping to classify antibiotics by resistance potential and pathogenic consequences. Applying this framework to Klebsiella pneumoniae identified functionally distinct antibiotic candidates associated with elevated virulence risk. Resistance evolution rapidly increased virulence through clinically-relevant mutations, without direct selection for pathogenicity. Despite distinct genetic routes, resistance converged on cell-envelope rewiring. A single resistance mutation increased epithelial adhesion, intracellular colonization, macrophage immune-evasion, and tissue persistence in murine infection models, transforming K. pneumoniae into a more invasive and cytotoxic pathogen. Risk-profile analysis revealed partial decoupling of resistance and pathogenicity, with some low-resistance antibiotics yielding highly-virulent populations. These findings establish resistance-driven virulence as an underappreciated translational hazard and call for incorporating host-pathogen interactions into resistance surveillance and preclinical antibiotic development.

microbiology↗

bioRxiv2025

Comprehensive Bulk and Single-Cell RNA Sequencing Uncovers Senescence-Associated Biomarkers in Therapeutic Mesenchymal Stem Cells

BackgroundMesenchymal stem cells (MSCs) hold great promise in cell therapy, but their effectiveness declines with repeated cell divisions due to senescence. Canines, sharing aging characteristics with humans, serve as a valuable model to study this process in a translational context. MethodsIn the present study, we performed an in-depth characterization of senescence in canine MSCs using a combination of morphological, molecular, and transcriptomic analyses. Early (P2) and late-passage (P6) canine MSCs were characterized using a combination of senescence-associated {beta}-galactosidase staining, cell cycle profiling, and both bulk and single-cell RNA sequencing to capture global transcriptional changes. ResultsBy employing a passage-based in vitro approach, the present study demonstrates that late-passage cells (P6) compared to early-passage cells (P2) exhibit hallmark features of senescence, including morphological alterations, elevated SA-{beta}-galactosidase activity, and considerable transcriptional changes. These changes were represented by significant upregulation of established senescence marker genes, alongside potential novel candidates and downregulation of genes associated with cell cycle progression and proliferation. Moreover, single-cell RNA sequencing uncovered heterogeneous distribution of senescent subpopulations, upregulation of SASP-related genes and reduced proliferation markers. ConclusionsOur findings demonstrate that combining classical markers with bulk and single-cell RNA sequencing facilitates senescent cell identification while improving quality control for clinical MSC samples.

cell biology↗

bioRxiv2023

The Medicago truncatula nodule-specific cysteine-rich peptides, NCR343 and NCR-new35 are required for the maintenance of rhizobia in nitrogen-fixing nodules.

In the nodules of Inverted Repeat-Lacking Clade legumes, including M. truncatula, nitrogen-fixing rhizobia undergo terminal differentiation resulting in elongated and endoreduplicated bacteroids specialised for nitrogen fixation. This irreversible transition of rhizobia is mediated by host produced nodule-specific cysteine-rich (NCR) peptides, of which about 700 are encoded in the M. truncatula genome. Some of these NCR peptides, NCR169, NCR211 and NCR247, are essential for nitrogen-fixing symbiosis. The analysis of bacteroid and symbiotic host cell differentiation revealed that the symbiotic phenotype of M. truncatula mutants, Mtsym19, Mtsym20 and NF-FN9363, were defective likewise in the formerly studied ncr mutants, Mtdnf4-1 and Mtdnf7-2. The incomplete differentiation of bacteroids triggered premature senescence of rhizobia in the nitrogen fixation zones of mutant nodules. Mtsym19 and Mtsym20 mutants are defective in the same peptide NCR-new35 and the lack of NCR343 is responsible for the ineffective symbiosis of NF-FN9363. The activity of NCR-new35 is significantly lower and limited to the transition zone of the nodule compared with other crucial NCRs. The fluorescent protein-tagged version of NCR343 and NCR-new35 localize to the symbiotic compartment. Our discovery added two additional members to the group of NCR genes essential for nitrogen-fixing symbiosis in M. truncatula.

plant biology↗