Flo11p, drug efflux pumps, and the extracellular matrix cooperate to form biofilm yeast colonies

Váchová, Libuše; Šťovíček, Vratislav; Hlaváček, Otakar; Chernyavskiy, Oleksandr; Štěpánek, Luděk; Kubínová, Lucie; Palková, Zdena

doi:10.1083/jcb.201103129

Cited by 87 publications

(127 citation statements)

References 47 publications

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“…Although most laboratory strains produce relatively unstructured "smooth" colonies, some natural isolates of S. cerevisiae produce colonies with complex multicellular features, such as folds, crevices, and channels that form as the colony grows on solid media (20,21). These "fluffy" colonies possess properties similar to those of microbial biofilms, including the secretion and maintenance of an extracellular matrix (21)(22)(23), localized expression of drug efflux pumps (23), increased adherence (24), and the use of cell-cell communication (25). Fluffy colony formation requires the function and coordination of numerous pathways that underlie the trait, and the deletion of key factors produces a smooth colony phenotype (26)(27)(28).…”

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confidence: 99%

Aneuploidy underlies a multicellular phenotypic switch

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Hays

Cromie

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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Although microorganisms are traditionally used to investigate unicellular processes, the yeast Saccharomyces cerevisiae has the ability to form colonies with highly complex, multicellular structures. Colonies with the "fluffy" morphology have properties reminiscent of bacterial biofilms and are easily distinguished from the "smooth" colonies typically formed by laboratory strains. We have identified strains that are able to reversibly toggle between the fluffy and smooth colony-forming states. Using a combination of flow cytometry and high-throughput restriction-site associated DNA tag sequencing, we show that this switch is correlated with a change in chromosomal copy number. Furthermore, the gain of a single chromosome is sufficient to switch a strain from the fluffy to the smooth state, and its subsequent loss to revert the strain back to the fluffy state. Because copy number imbalance of six of the 16 S. cerevisiae chromosomes and even a single gene can modulate the switch, our results support the hypothesis that the state switch is produced by dosage-sensitive genes, rather than a general response to altered DNA content. These findings add a complex, multicellular phenotype to the list of molecular and cellular traits known to be altered by aneuploidy and suggest that chromosome missegregation can provide a quick, heritable, and reversible mechanism by which organisms can toggle between phenotypes. colony morphology | copy number variation | phenotypic switching | bet-hedging

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confidence: 99%

Aneuploidy underlies a multicellular phenotypic switch

Tan

Hays

Cromie

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

106

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“…Recent studies have demonstrated that the budding yeast Saccharomyces forms microbial communities that have these biofilm characteristics (Kuthan et al 2003;Váchová et al 2011). These characteristics are present in mats that form on soft agar (Reynolds and Fink 2001) and in complex colony biofilms (sometimes referred to as "fluffy colonies") that are distinguished from nonbiofilm colonies (also described as simple or smooth colonies) by intricate, organized, and strain-specific architecture (Supporting Information, Figure S1) (Palková and Váchová 2006;Granek and Magwene 2010;Honigberg 2011).…”

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confidence: 99%

The Genetic Architecture of Biofilm Formation in a Clinical Isolate of Saccharomyces cerevisiae

et al. 2013

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Biofilms are microbial communities that form on surfaces. They are the primary form of microbial growth in nature and can have detrimental impacts on human health. Some strains of the budding yeast Saccharomyces cerevisiae form colony biofilms, and there is substantial variation in colony architecture between biofilm-forming strains. To identify the genetic basis of biofilm variation, we developed a novel version of quantitative trait locus mapping, which leverages cryptic variation in a clinical isolate of S. cerevisiae. We mapped 13 loci linked to heterogeneity in biofilm architecture and identified the gene most closely associated with each locus. Of these candidate genes, six are members of the cyclic AMP-protein kinase A pathway, an evolutionarily conserved cell signaling network. Principal among these is CYR1, which encodes the enzyme that catalyzes production of cAMP. Through a combination of gene expression measurements, cell signaling assays, and gene overexpression, we determined the functional effects of allelic variation at CYR1. We found that increased pathway activity resulting from protein coding and expression variation of CYR1 enhances the formation of colony biofilms. Four other candidate genes encode kinases and transcription factors that are targets of this pathway. The protein products of several of these genes together regulate expression of the sixth candidate, FLO11, which encodes a cell adhesion protein. Our results indicate that epistatic interactions between alleles with both positive and negative effects on cyclic AMP-protein kinase A signaling underlie much of the architectural variation we observe in colony biofilms. They are also among the first to demonstrate genetic variation acting at multiple levels of an integrated signaling and regulatory network. Based on these results, we propose a mechanistic model that relates genetic variation to gene network function and phenotypic outcomes. BIOFILMS are complex, surface-adherent communities of microbes. They are ubiquitous in nature and in the human environment (Donlan and Costerton 2002;López et al. 2010). Not only can they be life threatening when they form in the human body (Hall-Stoodley et al. 2004), but biofilms also create problems when they form on human-made structures, ranging from merely annoying (shower curtains) to hazardous (nuclear power plants) (Flemming 2002). Because of the frequency with which we interact with biofilms, characterizing the cellular mechanisms that regulate them and understanding the genetic basis of their variation are of great interest.The ability to form biofilms is a multifactorial trait, resulting from the interactions of several lower-level properties, including cell-cell and cell-substrate adhesion; production of extracellular matrix; and spatial heterogeneity in cell morphology, growth, and division. Recent studies have demonstrated that the budding yeast Saccharomyces forms microbial communities that have these biofilm characteristics (Kuthan et al. 2003;Váchová et al. 2011). These ch...

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“…Using x-ray computed tomography, they have shown that this biofilm can also be impenetrable to gas. In another study, Váchová et al [71] showed that wild yeast biofilms can develop drug resistance "in which specialized cells jointly execute multiple protection strategies." In particular, their analysis shows that the cells selectively create permeable EPS, while coordinated efflux pumps actively expel toxic substances outside the cell clusters.…”

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confidence: 99%

Hydrodynamic dispersion within porous biofilms

et al. 2013

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OATAO is an open access repository that collects the work of Toulouse researchers and makes it freely available over the web where possible. Many microorganisms live within surface-associated consortia, termed biofilms, that can form intricate porous structures interspersed with a network of fluid channels. In such systems, transport phenomena, including flow and advection, regulate various aspects of cell behavior by controlling nutrient supply, evacuation of waste products, and permeation of antimicrobial agents. This study presents multiscale analysis of solute transport in these porous biofilms. We start our analysis with a channel-scale description of mass transport and use the method of volume averaging to derive a set of homogenized equations at the biofilm-scale in the case where the width of the channels is significantly smaller than the thickness of the biofilm. We show that solute transport may be described via two coupled partial differential equations or telegrapher's equations for the averaged concentrations. These models are particularly relevant for chemicals, such as some antimicrobial agents, that penetrate cell clusters very slowly. In most cases, especially for nutrients, solute penetration is faster, and transport can be described via an advection-dispersion equation. In this simpler case, the effective diffusion is characterized by a second-order tensor whose components depend on (1) the topology of the channels' network; (2) the solute's diffusion coefficients in the fluid and the cell clusters; (3) hydrodynamic dispersion effects; and (4) an additional dispersion term intrinsic to the two-phase configuration. Although solute transport in biofilms is commonly thought to be diffusion dominated, this analysis shows that hydrodynamic dispersion effects may significantly contribute to transport.

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Flo11p, drug efflux pumps, and the extracellular matrix cooperate to form biofilm yeast colonies

Abstract: Biofilm yeast colonies are complex structures that form through cooperative action of constituent cells and provide a protective environment for cell growth.

Cited by 87 publications

References 47 publications

Aneuploidy underlies a multicellular phenotypic switch

Aneuploidy underlies a multicellular phenotypic switch

The Genetic Architecture of Biofilm Formation in a Clinical Isolate of Saccharomyces cerevisiae

Hydrodynamic dispersion within porous biofilms

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