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LAM Genes Contribute to Environmental Stress Tolerance but Sensibilize Yeast Cells to Azoles.

ABSTRACT: Lam proteins transport sterols between the membranes of different cellular compartments. In Saccharomyces cerevisiae, the LAM gene family consists of three pairs of paralogs. Because the function of paralogous genes can be redundant, the phenotypes of only a small number of LAM gene deletions have been reported; thus, the role of these genes in yeast physiology is still unclear. Here, we surveyed the phenotypes of double and quadruple deletants of paralogous LAM2(YSP2)/LAM4 and LAM1(YSP1)/LAM3(SIP3) genes that encode proteins localized in the junctions of the plasma membrane and endoplasmic reticulum. The quadruple deletant showed increased sterol content and a strong decrease in ethanol, heat shock and high osmolarity resistance. Surprisingly, the quadruple deletant and LAM2/LAM4 double deletion strain showed increased tolerance to the azole antifungals clotrimazole and miconazole. This effect was not associated with an increased rate of ABC-transporter substrate efflux. Possibly, increased sterol pool in the LAM deletion strains postpones the effect of azoles on cell growth. Alternatively, LAM deletions might alleviate the toxic effect of sterols as Lam proteins can transport toxic sterol biosynthesis intermediates into membrane compartments that are sensitive to these compounds. Our findings reveal novel biological roles of LAM genes in stress tolerance and suggest that mutations in these genes may confer upregulation of a mechanism that provides resistance to azole antifungals in pathogenic fungi.

SUBMITTER: Sokolov SS

PROVIDER: S-EPMC6997477 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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LAM Genes Contribute to Environmental Stress Tolerance but Sensibilize Yeast Cells to Azoles.

Sokolov Svyatoslav S SS Vorobeva Margarita A MA Smirnova Alexandra I AI Smirnova Ekaterina A EA Trushina Nataliya I NI Galkina Kseniia V KV Severin Fedor F FF Knorre Dmitry A DA

Frontiers in microbiology 20200128

Lam proteins transport sterols between the membranes of different cellular compartments. In Saccharomyces cerevisiae, the LAM gene family consists of three pairs of paralogs. Because the function of paralogous genes can be redundant, the phenotypes of only a small number of LAM gene deletions have been reported; thus, the role of these genes in yeast physiology is still unclear. Here, we surveyed the phenotypes of double and quadruple deletants of paralogous LAM2(YSP2)/LA ...[more]

PMID: 32047490

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Project description:The contribution of stress protein duplication and deletion events to the evolution of the Aspergilli was studied. We performed a large-scale homology analysis of stress proteins and generated and analysed three stress defence system models based on Saccharomyces cerevisiae, Schizosaccharomyces pombe and Aspergillus nidulans. Although both yeast-based and A. nidulans-based models were suitable to trace evolutionary changes, the A. nidulans-based model performed better in mapping stress protein radiations. The strong Mantel correlation found between the positions of species in the phylogenetic tree on the one hand and either in the A. nidulans-based or S. cerevisiae-based models on the other hand demonstrated that stress protein expansions and reductions contributed significantly to the evolution of the Aspergilli. Interestingly, stress tolerance attributes correlated well with the number of orthologs only for a few stress proteins. Notable examples are Ftr1 iron permease and Fet3 ferro-O2-oxidoreductase, elements of the reductive iron assimilation pathway, in the S. cerevisiae-based model, as well as MpkC, a HogA-like mitogen activated protein kinase in the A. nidulans-based model. In the case of the iron assimilation proteins, the number of orthologs showed a positive correlation with H2O2-induced stress tolerance while the number of MpkC orthologs correlated positively with Congo Red induced cell wall stress, sorbitol induced osmotic stress and H2O2 induced oxidative stress tolerances. For most stress proteins, changes in the number of orthologs did not correlate well with any stress tolerance attributes. As a consequence, stress tolerance patterns of the studied Aspergilli did not correlate with either the sets of stress response proteins in general or with the phylogeny of the species studied. These observations suggest that stress protein duplication and deletion events significantly contributed to the evolution of stress tolerance attributes of Aspergilli. In contrast, there are other processes, which may counterbalance the effects of stress gene duplications or deletions including (i) alterations in the structures of stress proteins leading to changes in their biological activities, (ii) varying biosynthesis of stress proteins, (iii) rewiring stress response regulatory networks or even (iv) acquiring new stress response genes by horizontal gene transfer. All these multilevel changes are indispensable for the successful adaptation of filamentous fungi to altering environmental conditions, especially when these organisms are entering new ecological niches.

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LAM Genes Contribute to Environmental Stress Tolerance but Sensibilize Yeast Cells to Azoles.

Publications

<i>LAM</i> Genes Contribute to Environmental Stress Tolerance but Sensibilize Yeast Cells to Azoles.

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