Thoughts on Quorum Sensing and Fungal Dimorphism

Nickerson, Kenneth W.; Atkin, Audrey L.; Hargarten, Jessica C.; Pathirana, Ruvini U.; Hasim, Sahar

doi:10.1007/978-94-007-4264-2_12

Cited by 7 publications

(5 citation statements)

References 48 publications

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“…Farnesol is a precursor of the synthesis of sterols in C. albicans (Hornby et al ., 2001; Nickerson et al ., 2013). Ergosterol (ergosta‐5,7,22‐trien‐3β‐ol) is a sterol found in fungi and is an essential component of fungal cell membranes (Weete et al ., 2010).…”

Section: Resultsmentioning

confidence: 99%

“…These results show that these medium-chain fatty acids, but not long fatty acids, negatively influenced the synthesis of farnesol. Farnesol is a precursor of the synthesis of sterols in C. albicans (Hornby et al, 2001;Nickerson et al, 2013). Ergosterol (ergosta-5,7,22-trien-3b-ol) is a sterol found in fungi and is an essential component of fungal cell membranes (Weete et al, 2010).…”

Section: Medium-chain Fatty Acids Decreased the Productions Of Farnesmentioning

confidence: 99%

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Antibiofilm and antifungal activities of medium‐chain fatty acids against Candida albicans via mimicking of the quorum‐sensing molecule farnesol

Lee

Kim

Khadke

2020

Microbial Biotechnology

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Candida biofilms are tolerant to conventional antifungal therapeutics and the host immune system. The transition of yeast cells to hyphae is considered a key step in C. albicans biofilm development, and this transition is inhibited by the quorum-sensing molecule farnesol. We hypothesized that fatty acids mimicking farnesol might influence hyphal and biofilm formation by C. albicans. Among 31 saturated and unsaturated fatty acids, six medium-chain saturated fatty acids, that is, heptanoic acid, octanoic acid, nonanoic acid, decanoic acid, undecanoic acid and lauric acid, effectively inhibited C. albicans biofilm formation by more than 75% at 2 µg ml À1 with MICs in the range 100-200 µg ml À1. These six fatty acids at 2 µg ml À1 and farnesol at 100 µg ml À1 inhibited hyphal growth and cell aggregation. The addition of fatty acids to C. albicans cultures decreased the productions of farnesol and sterols. Furthermore, downregulation of several hyphal and biofilm-related genes caused by heptanoic or nonanoic acid closely resembled the changes caused by farnesol. In addition, nonanoic acid, the most effective compound diminished C. albicans virulence in a Caenorhabditis elegans model. Our results suggest that mediumchain fatty acids inhibit more effectively hyphal growth and biofilm formation than farnesol.

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Section: Resultsmentioning

confidence: 99%

Section: Medium-chain Fatty Acids Decreased the Productions Of Farnesmentioning

confidence: 99%

Antibiofilm and antifungal activities of medium‐chain fatty acids against Candida albicans via mimicking of the quorum‐sensing molecule farnesol

Lee

Kim

Khadke

2020

Microbial Biotechnology

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“…It is tempting to speculate, that Eed1 may regulate farnesol production, secretion and/or sensing in C. albicans , as increased secretion will lower intracellular farnesol levels and may in turn promote an increased farnesol production. However, increased farnesol sensitivity may also result from differential diffusion due to general membrane changes, or from decreased farnesol inactivation, by degradation or modification of the molecule to a substance with lower activity (Shchepin et al ., ; Nickerson et al ., ).…”

Section: Discussionmentioning

confidence: 97%

A functional link between hyphal maintenance and quorum sensing in Candida albicans

Polke

Sprenger

Scherlach

et al. 2016

Molecular Microbiology

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Morphogenesis in Candida albicans requires hyphal initiation and maintenance, and both processes are regulated by the fungal quorum sensing molecule (QSM) farnesol. We show that deletion of C. albicans EED1, which is crucial for hyphal extension and maintenance, led to a dramatically increased sensitivity to farnesol, and thus identified the first mutant hypersensitive to farnesol. Furthermore, farnesol decreased the transient filamentation of an eed1Δ strain without inducing cell death, indicating that two separate mechanisms mediate quorum sensing and cell lysis by farnesol. To analyze the cause of farnesol hypersensitivity we constructed either hyperactive or deletion mutants of factors involved in farnesol signaling, by introducing the hyperactive RAS1 or pADH1-CYR1 allele, or deleting CZF1 or NRG1 respectively. Neither of the constructs nor the exogenous addition of dB-cAMP was able to rescue the farnesol hypersensitivity, highlighting that farnesol mediates its effects not only via the cAMP pathway. Interestingly, the eed1Δ strain also displayed increased farnesol production. When eed1Δ was grown under continuous medium flow conditions, to remove accumulating QSMs from the supernatant, maintenance of eed1Δ filamentation, although not restored, was significantly prolonged, indicating a link between farnesol sensitivity, production, and the hyphal maintenance-defect in the eed1Δ mutant strain.

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“…Results were not directly comparable, leading to questions of whether gene expression is influenced by local factors. One potential factor that is noted in the Candida literature is water quality, which despite modern purification systems, may vary widely and influence biological function of fungal cells (Nickerson et al, 2012). Neale et al (2018) measured expression of the five C. parapsilosis ALS genes using a SYBR Green-based method.…”

Section: Discussionmentioning

confidence: 99%

Agglutinin-Like Sequence (ALS) Genes in the Candida parapsilosis Species Complex: Blurring the Boundaries Between Gene Families That Encode Cell-Wall Proteins

Smith

Miller

et al. 2019

Front. Microbiol.

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The agglutinin-like sequence (Als) proteins are best-characterized in Candida albicans and known for their role in adhesion of the fungal cell to host and abiotic surfaces. ALS sequences are often misassembled in whole-genome sequence data because each species has multiple ALS loci that contain similar sequences, most notably tandem copies of highly conserved repeated sequences. The Candida parapsilosis species complex includes Candida parapsilosis , Candida orthopsilosis , and Candida metapsilosis , three distinct but closely related species. Using publicly available genome resources, de novo genome assemblies, and laboratory experimentation including Sanger sequencing, five ALS genes were characterized in C. parapsilosis strain CDC317, three in C. orthopsilosis strain 90–125, and four in C. metapsilosis strain ATCC 96143. The newly characterized ALS genes shared similar features with the well-known C. albicans ALS family, but also displayed unique attributes such as novel short, imperfect repeat sequences that were found in other genes encoding fungal cell-wall proteins. Evidence of recombination between ALS sequences and other genes was most obvious in CmALS2265 , which had the 5′ end of an ALS gene and the repeated sequences and 3′ end from the IFF/HYR family. Together, these results blur the boundaries between the fungal cell-wall families that were defined in C. albicans . TaqMan assays were used to quantify relative expression for each ALS gene. Some measurements were complicated by the assay location within the ALS gene. Considerable variation was noted in relative gene expression for isolates of the same species. Overall, however, there was a trend toward higher relative gene expression in saturated cultures rather than younger cultures. This work provides a complete description of the ALS genes in the C. parapsilosis species complex and a toolkit that promotes further investigations into the role of the Als proteins in host-fungal interactions.

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Thoughts on Quorum Sensing and Fungal Dimorphism

Cited by 7 publications

References 48 publications

Antibiofilm and antifungal activities of medium‐chain fatty acids against Candida albicans via mimicking of the quorum‐sensing molecule farnesol

Antibiofilm and antifungal activities of medium‐chain fatty acids against Candida albicans via mimicking of the quorum‐sensing molecule farnesol

A functional link between hyphal maintenance and quorum sensing in Candida albicans

Agglutinin-Like Sequence (ALS) Genes in the Candida parapsilosis Species Complex: Blurring the Boundaries Between Gene Families That Encode Cell-Wall Proteins

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