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Nadir, H.

Publications and source records attributed to Nadir, H..

2 recordsLinked to original sources

HaloUMI: Physics-informed analysis of inhibition halo assays

Quantification of microbial growth inhibition is central to assays from antibiotic susceptibility to antifungal sensitivity, yet existing approaches struggle with irregular inhibition zones and variation in microbial lawn density. Here, we present Halo Unbiased Measurement of growth Inhibition (HaloUMI), an open-source Python graphical interface for automated, high-throughput analysis of lawn-based microbial assays. HaloUMI integrates robust image processing with physics-informed modelling to quantify inhibition zones without assuming circular geometry, enabling analysis of uniform and irregular halo phenotypes. Using diffusion- and growth-based physical modelling, HaloUMI experimentally validates a correction for variation in microbial lawn density, a major source of assay variability that can confound quantitative comparison of inhibition phenotypes. Validation using simulations and yeast killer-toxin assays demonstrates precise, reproducible measurement across diverse conditions. HaloUMI is applicable to multiple assay formats, including microbial interaction, mating, and conventional disc-diffusion assays, providing an accessible and generalisable framework for quantitative analysis of microbial growth inhibition.

biophysics↗

Killer Toxin K28 resistance in yeast relies on COG complex mediated trafficking of the defence factor Ktd1

A/B toxins are a diverse family of protein toxins that enter host cells via endocytosis and induce cell death. In yeast, the A/B toxin K28 is internalised to endosomes of susceptible yeast, before following the retrograde trafficking pathway and ultimately triggering cell cycle arrest. The endolysosomal defence factor Ktd1 protects against K28, but its regulation remains unclear. Cog7, a subunit of the conserved oligomeric Golgi (COG) tethering complex, has been implicated in K28 defence, though the mechanism is unknown. We developed a high throughput K28 sensitivity assay and bespoke analysis package to show that all lobe B COG subunits (Cog5 - 8) are required for K28 resistance. Although the COG complex modulates glycosylation of the surface molecules required to bind extracellular K28, our experiments reveal that the hypersensitivity of cog mutants is primarily explained by defects in Ktd1 trafficking. Ktd1 mis-localisation in cog mutants is reminiscent to disruptions in Snc1, a surface cargo that recycles multiple times via the Golgi. This work suggests not only that the COG complex is responsible for the precise trafficking Ktd1 required to mediate toxin defence, but that Ktd1 may survey endolysosomal compartments for internalised K28. This work underpins the importance of Ktd1 in defence against the A/B toxin K28, and implies various membrane trafficking regulators might influence toxin effects in other eukaryotic systems.

cell biology↗