Quantifying the dominant growth mechanisms of dimorphic yeast using a lattice-based model

Abstract

A mathematical model is presented for the growth of yeast that incorporates both dimorphic behaviour and nutrient diffusion. The budding patterns observed in the standard and pseudohyphal growth modes are represented by a bias in the direction of cell proliferation. A set of spatial indices is developed to quantify the morphology and compare the relative importance of the directional bias to nutrient concentration and diffusivity on colony shape. It is found that there are three different growth modes: uniform growth, diffusion-limited growth (DLG) and an intermediate region in which the bias determines the morphology. The dimorphic transition due to nutrient limitation is investigated by relating the directional bias to the nutrient concentration, and this is shown to replicate the behaviour observed Comparisons are made with experimental data, from which it is found that the model captures many of the observed features. Both DLG and pseudohyphal growth are found to be capable of generating observed experimental morphologies.

Diffusion-Limited Growth of Microbial Colonies

“…subtilis 1 , and ( c ) S . cerevisiae 31 . The petri dishes shown (a and b) were 88 mm in diameter, while the scale bar ( c ) represents 2 mm.…”

“…While this work went some way towards quantifying colony growth, no attempt was made to quantify the behaviour of repelling colonies or directed growth. A limited number of studies have modelled the growth of yeast colonies specifically 31 – 34 ; however, the extent to which DLG influences yeast colony morphology has not yet been thoroughly investigated.…”

“…While the cell aspect ratio of dimorphic yeast provides a visual indication that the colony has entered the pseudohyphal growth mode, the low resolution of typical experimental images means that the cell aspect ratios are generally not known and thus it is not even possible to identify whether a yeast colony has entered the pseudohyphal growth mode from a single image alone. Previous mathematical studies have shown that the morphology of non-uniform yeast colonies can be reproduced using either DLG or the pseudohyphal budding pattern 31 . There is thus a need to develop a framework for identifying the dominant growth mechanisms that does not rely on observations of individual cells.…”

TAMMiCol: Tool for analysis of the morphology of microbial colonies

“…These features are usually investigated via two-dimensional top-down images of colonies grown on a solid medium [1, 5–7]. The growth patterns observed in these experimental images are typically quantified using binary versions of the images, which indicate whether or not each pixel is part of the colony [7–9]. While it is possible to manually convert a single image to binary with sufficient accuracy using image analysis software, this task is difficult in studies of dimorphic growth, which may involve hundreds of images [7], and is infeasible for large datasets produced using genome-wide mutant libraries, which consist of thousands of images [6].…”

Characterizing the shape patterns of dimorphic yeast pseudohyphae

“…The fractal dimension has been shown to quantify the morphologies of bacterial colonies, which possess similar colony morphologies to yeast [ 11 , 12 ]. The shape patterns in yeast colonies have been quantified using indices derived from normalized count functions and pair correlation functions, which have the advantage of providing information on the spatial distribution of the cells [ 7 , 13 ]. These studies led to successful quantification of spatial patterns in binary images of S. cerevisiae colonies exhibiting pseudohyphal and invasive growth; however, little work has been done to classify binary images of yeast colonies by strain or nutrient level based on the spatial patterns observed in these images.…”