The resistance of the yeast Saccharomyces cerevisiae to the biocide polyhexamethylene biguanide: involvement of cell wall integrity pathway and emerging role for YAP1

Polyhexamethylene biguanide (PHMB) is an antiseptic polymer that is mainly used for cleaning hospitals and pools and combating Acantamoeba infection. Its fungicide activity was recently shown by its lethal effect on yeasts that contaminate the industrial ethanol process, and on the PE-2 strain of Sa...

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Published in:	BMC molecular biology Vol. 12; no. 1; p. 38
Main Authors:	Elsztein, Carolina, de Lucena, Rodrigo M, de Morais, Jr, Marcos A
Format:	Journal Article
Language:	English
Published:	England BioMed Central Ltd 19-08-2011 BioMed Central
Subjects:	Bacteria Biguanides Biguanides - pharmacology Binding sites Brewer's yeast Cell Wall - drug effects Cell Wall - metabolism Disinfectants - pharmacology Disinfection & disinfectants Drug Resistance, Fungal - physiology E coli Gene Expression Genetic aspects Genomes Microbiology Physiological aspects Plant cell walls Polymerase chain reaction Promoter Regions, Genetic Proteins Saccharomyces cerevisiae - cytology Saccharomyces cerevisiae - drug effects Saccharomyces cerevisiae - physiology Saccharomyces cerevisiae Proteins - genetics Saccharomyces cerevisiae Proteins - metabolism Signal Transduction - drug effects Stress response Transcription Factors - genetics Transcription Factors - metabolism Yeast Brazil
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Summary:	Polyhexamethylene biguanide (PHMB) is an antiseptic polymer that is mainly used for cleaning hospitals and pools and combating Acantamoeba infection. Its fungicide activity was recently shown by its lethal effect on yeasts that contaminate the industrial ethanol process, and on the PE-2 strain of Saccharomyces cerevisiae, one of the main fermenting yeasts in Brazil. This pointed to the need to know the molecular mechanism that lay behind the cell resistance to this compound. In this study, we examined the factors involved in PHMB-cell interaction and the mechanisms that respond to the damage caused by this interaction. To achieve this, two research strategies were employed: the expression of some genes by RT-qPCR and the analysis of mutant strains. Cell Wall integrity (CWI) genes were induced in the PHMB-resistant Saccharomyces cerevisiae strain JP-1, although they are poorly expressed in the PHMB-sensitive Saccharomyces cerevisiae PE2 strain. This suggested that PHMB damages the glucan structure on the yeast cell wall. It was also confirmed by the observed sensitivity of the yeast deletion strains, Δslg1, Δrom2, Δmkk2, Δslt2, Δknr4, Δswi4 and Δswi4, which showed that the protein kinase C (PKC) regulatory mechanism is involved in the response and resistance to PHMB. The sensitivity of the Δhog1 mutant was also observed. Furthermore, the cytotoxicity assay and gene expression analysis showed that the part played by YAP1 and CTT1 genes in cell resistance to PHMB is unrelated to oxidative stress response. Thus, we suggested that Yap1p can play a role in cell wall maintenance by controlling the expression of the CWI genes. The PHMB treatment of the yeast cells activates the PKC1/Slt2 (CWI) pathway. In addition, it is suggested that HOG1 and YAP1 can play a role in the regulation of CWI genes.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	1471-2199 1471-2199
DOI:	10.1186/1471-2199-12-38