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Fitzpatrick, David A.; Logue, Mary E.; Stajich, Jason E.; Butler, Geraldine

doi:10.1186/1471-2148-6-99

Cited by 407 publications

(222 citation statements)

References 90 publications

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“…Figure 5 shows similar levels of biocidal activity against C. albicans and C. parapsilosis but less activity against C. glabrata, with about 50% surviving after 15 min of exposure. This result is consistent with the fact that C. albicans and C. parapsilosis share a closer phylogenetic relationship than is found between C. albicans and C. glabrata (36).…”

Section: Resultssupporting

confidence: 81%

Antifungal Properties of Cationic Phenylene Ethynylenes and Their Impact on β-Glucan Exposure

Pappas

Sylejmani

Graus

et al. 2016

Antimicrob Agents Chemother

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Candida species are the cause of many bloodstream infections through contamination of indwelling medical devices. These infections account for a 40% mortality rate, posing a significant risk to immunocompromised patients. Traditional treatments against Candida infections include amphotericin B and various azole treatments. Unfortunately, these treatments are associated with high toxicity, and resistant strains have become more prevalent. As a new frontier, light-activated phenylene ethynylenes have shown promising biocidal activity against Gram-positive and -negative bacterial pathogens, as well as the environmental yeast Saccharomyces cerevisiae. In this study, we monitored the viability of Candida species after treatment with a cationic conjugated polymer [poly(p-phenylene ethynylene); PPE] or oligomer ["end-only" oligo(p-phenylene ethynylene); EO-OPE] by flow cytometry in order to explore the antifungal properties of these compounds. The oligomer was found to disrupt Candida albicans yeast membrane integrity independent of light activation, while PPE is able to do so only in the presence of light, allowing for some control as to the manner in which cytotoxic effects are induced. The contrast in killing efficacy between the two compounds is likely related to their size difference and their intrinsic abilities to penetrate the fungal cell wall. Unlike EO-OPE-DABCO (where DABCO is quaternized diazabicyclo[2,2,2]octane), PPE-DABCO displayed a strong propensity to associate with soluble ␤-glucan, which is expected to inhibit its ability to access and perturb the inner cell membrane of Candida yeast. Furthermore, treatment with PPE-DABCO unmasked Candida albicans ␤-glucan and increased phagocytosis by Dectin-1-expressing HEK-293 cells. In summary, cationic phenylene ethynylenes show promising biocidal activity against pathogenic Candida yeast cells while also exhibiting immunostimulatory effects.

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Section: Resultssupporting

confidence: 81%

Antifungal Properties of Cationic Phenylene Ethynylenes and Their Impact on β-Glucan Exposure

Pappas

Sylejmani

Graus

et al. 2016

Antimicrob Agents Chemother

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“…3A) is not yet conclusively established (66). We therefore repeated the analysis using a multifurcation at this node and found similar results regarding the asymmetry, but observed variation in the estimates of CDK consensus gain and loss events on each branch (data not shown).…”

Section: Methodsmentioning

confidence: 62%

“…Although the current view supports the clade containing K. lactis, Ashbya gossypii, Kluveromyces waltii, and Saccharomyces kluyveri as a sister to the clade containing S. cerevisiae (65,66) the placement of the species (Fig. 3A) is not yet conclusively established (66).…”

Section: Methodsmentioning

confidence: 65%

Regulatory evolution in proteins by turnover and lineage-specific changes of cyclin-dependent kinase consensus sites

Moses

Liku²,

et al. 2007

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

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Evolutionary change in gene regulation is a key mechanism underlying the genetic component of organismal diversity. Here, we study evolution of regulation at the posttranslational level by examining the evolution of cyclin-dependent kinase (CDK) consensus phosphorylation sites in the protein subunits of the prereplicative complex (RC). The pre-RC, an assembly of proteins formed during an early stage of DNA replication, is believed to be regulated by CDKs throughout the animals and fungi. Interestingly, although orthologous pre-RC components often contain clusters of CDK consensus sites, the positions and numbers of sites do not seem conserved. By analyzing protein sequences from both distantly and closely related species, we confirm that consensus sites can turn over rapidly even when the local cluster of sites is preserved, consistent with the notion that precise positioning of phosphorylation events is not required for regulation. We also identify evolutionary changes in the clusters of sites and further examine one replication protein, Mcm3, where a cluster of consensus sites near a nucleocytoplasmic transport signal is confined to a specific lineage. We show that the presence or absence of the cluster of sites in different species is associated with differential regulation of the transport signal. These findings suggest that the CDK regulation of MCM nuclear localization was acquired in the lineage leading to Saccharomyces cerevisiae after the divergence with Candida albicans. Our results begin to explore the dynamics of regulatory evolution at the posttranslational level and show interesting similarities to recent observations of regulatory evolution at the level of transcription.DNA replication ͉ MCM3 ͉ phosphorylation T he contribution of regulatory evolution to biological diversity is increasingly well appreciated (1-4). The identification of changes in transcriptional regulatory proteins (5, 6) and, more frequently, the cis-elements they recognize in noncoding DNA (reviewed in ref. 7), has provided mechanistic insight into the evolution of gene regulation.Genes are regulated at multiple levels, however. In eukaryotes, posttranslational regulation of protein activity by phosphorylation is of particular importance (8). Although little is known in general about the evolution of this type of regulation, comparative studies of posttranslational modification sites in phosphorylase (9, 10) and fructose 1-6-bisphosphatase (11) revealed that they were not conserved between homologues.Recent studies have applied computational approaches to databases of protein sequences to perform comparative studies on larger scales. For example, targets of protein kinase A were predicted based on conservation of consensus sites between Candida albicans and Saccharomyces cerevisiae (12). Another study examined regulation of cell-cycle proteins in four species and proposed coevolution between posttranslational regulation by phosphorylation and transcriptional regulation (13).Phosphoregulation plays a critical role in cell-cycle c...

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“…The protein, coding, and genomic sequences for the recently sequenced post-WGD species, K. polysporus, are from Scannell et al (2007). Sequences for the other species were downloaded from the Fungal Comparative Genomics database (http:// (Fitzpatrick et al 2006) and the National Center for Biotechnology Information (http:// www.ncbi.nlm.nih.gov/).…”

Section: Sequence Datamentioning

confidence: 99%

Relaxation of yeast mitochondrial functions after whole-genome duplication

Jiang¹,

Guan²,

Pinney³

et al. 2008

Genome Res.

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Mitochondria are essential for cellular energy production in most eukaryotic organisms. However, when glucose is abundant, yeast species that underwent whole-genome duplication (WGD) mostly conduct fermentation even under aerobic conditions, and most can survive without a functional mitochondrial genome. In this study, we show that the rate of evolution for the nuclear-encoded mitochondrial genes was greater in post-WGD species than pre-WGD species. Furthermore, codon usage bias was relaxed for these genes in post-WGD yeast species. The codon usage pattern and the distribution of a particular transcription regulatory element suggest that the change to an efficient aerobic fermentation lifestyle in this lineage might have emerged after WGD between the divergence of Kluyveromyces polysporus and Saccharomyces castellii from their common ancestor. This new energy production strategy could have led to the relaxation of mitochondrial function in the relevant yeast species.

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Cited by 407 publications

References 90 publications

Antifungal Properties of Cationic Phenylene Ethynylenes and Their Impact on β-Glucan Exposure

Antifungal Properties of Cationic Phenylene Ethynylenes and Their Impact on β-Glucan Exposure

Regulatory evolution in proteins by turnover and lineage-specific changes of cyclin-dependent kinase consensus sites

Relaxation of yeast mitochondrial functions after whole-genome duplication

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