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1.
Open Biol ; 10(12): 200343, 2020 12.
Article in English | MEDLINE | ID: mdl-33352067

ABSTRACT

Protein phosphatase 4 (PP4) is an evolutionarily conserved and essential Ser/Thr phosphatase that regulates cell division, development and DNA repair in eukaryotes. The major form of PP4, present from yeast to human, is the PP4c-R2-R3 heterotrimeric complex. The R3 subunit is responsible for substrate-recognition via its EVH1 domain. In typical EVH1 domains, conserved phenylalanine, tyrosine and tryptophan residues form the specific recognition site for their target's proline-rich sequences. Here, we identify novel binding partners of the EVH1 domain of the Drosophila R3 subunit, Falafel, and demonstrate that instead of binding to proline-rich sequences this EVH1 variant specifically recognizes atypical ligands, namely the FxxP and MxPP short linear consensus motifs. This interaction is dependent on an exclusively conserved leucine that replaces the phenylalanine invariant of all canonical EVH1 domains. We propose that the EVH1 domain of PP4 represents a new class of the EVH1 family that can accommodate low proline content sequences, such as the FxxP motif. Finally, our data implicate the conserved Smk-1 domain of Falafel in target-binding. These findings greatly enhance our understanding of the substrate-recognition mechanisms and function of PP4.


Subject(s)
Binding Sites , Conserved Sequence , Phosphoprotein Phosphatases/chemistry , Phosphoprotein Phosphatases/metabolism , Protein Interaction Domains and Motifs , Amino Acid Motifs , Amino Acid Sequence , Animals , Humans , Phosphoprotein Phosphatases/genetics , Protein Binding , Structure-Activity Relationship
2.
Biomed Res Int ; 2015: 398045, 2015.
Article in English | MEDLINE | ID: mdl-26366412

ABSTRACT

To better understand the molecular events underlying vulvovaginal candidiasis, we established an in vitro system. Immortalized vaginal epithelial cells were infected with live, yeast form C. albicans and C. albicans cultured in the same medium without vaginal epithelial cells were used as control. In both cases a yeast to hyphae transition was robustly induced. Whole transcriptome sequencing was used to identify specific gene expression changes in C. albicans. Numerous genes leading to a yeast to hyphae transition and hyphae specific genes were upregulated in the control hyphae and the hyphae in response to vaginal epithelial cells. Strikingly, the GlcNAc pathway was exclusively triggered by vaginal epithelial cells. Functional analysis in our in vitro system revealed that the GlcNAc biosynthesis is involved in the adherence to, and the ability to kill, vaginal epithelial cells in vitro, thus indicating the key role for this pathway in the virulence of C. albicans upon vulvovaginal candidiasis.


Subject(s)
Acetylglucosamine/metabolism , Candida albicans/metabolism , Candida albicans/pathogenicity , Epithelial Cells/microbiology , Vagina/microbiology , Virulence/physiology , Candidiasis, Vulvovaginal/microbiology , Cell Line , Epithelium/microbiology , Female , Humans , Hyphae/metabolism , Hyphae/pathogenicity
3.
Biomed Res Int ; 2014: 320796, 2014.
Article in English | MEDLINE | ID: mdl-25243129

ABSTRACT

The increasing number of multidrug-resistant microbes now emerging necessitates the identification of novel antimicrobial agents. Plants produce a great variety of antimicrobial peptides including hundreds of small, nodule-specific cysteine-rich NCR peptides that, in the legume Medicago truncatula, govern the differentiation of endosymbiotic nitrogen fixing bacteria and, in vitro, can display potent antibacterial activities. In this study, the potential candidacidal activity of 19 NCR peptides was investigated. Cationic NCR peptides having an isoelectric point above 9 were efficient in killing Candida albicans, one of the most common fungal pathogens of humans. None of the tested NCR peptides were toxic for immortalized human epithelial cells at concentrations that effectively killed the fungus; however, at higher concentrations, some of them inhibited the division of the cells. Furthermore, the cationic peptides successfully inhibited C. albicans induced human epithelial cell death in an in vitro coculture model. These results highlight the therapeutic potential of cationic NCR peptides in the treatment of candidiasis.


Subject(s)
Candida albicans/drug effects , Candidiasis/microbiology , Epithelial Cells/microbiology , Medicago truncatula/chemistry , Peptides/pharmacology , Antifungal Agents/pharmacology , Candida albicans/cytology , Candidiasis/pathology , Cations/pharmacology , Cell Death/drug effects , Cell Line , Cell Line, Transformed , Cell Membrane Permeability/drug effects , Cell Proliferation/drug effects , Cell Survival/drug effects , Epithelial Cells/drug effects , Epithelial Cells/pathology , Female , Humans , Microbial Sensitivity Tests , Symbiosis , Time Factors
4.
Genome Announc ; 1(3)2013 Jun 27.
Article in English | MEDLINE | ID: mdl-23792747

ABSTRACT

Propionibacterium avidum is an anaerobic Gram-positive bacterium that forms part of the normal human cutaneous microbiota, colonizing moist areas such as the vestibule of the nose, axilla, and perineum. Here we present the complete genome sequence of P. avidum strain 44067, which was isolated from a carbuncle of the trunk.

5.
Med Mycol ; 47(3): 331-5, 2009 May.
Article in English | MEDLINE | ID: mdl-18798117

ABSTRACT

The in vitro antifungal activities of two phenothiazine (PTZ) compounds, trifluoperazine (TFP) and chlorpromazine (CPZ) separately and in combination with amphotericin B (AMB) were tested against eight fungal isolates known to be possible agents of rhinocerebral zygomycosis. While both PTZs individually had antifungal effects against these filamentous fungi, only the antifungal activity of TFP increased in presence of AMB. TFP and AMB acted synergistically and caused full inhibition of all strains tested except for Absidia glauca. In contrast, CPZ was found to act antagonistically with AMB with all of studied isolates.


Subject(s)
Amphotericin B/pharmacology , Antifungal Agents/pharmacology , Chlorpromazine/pharmacology , Fungi/drug effects , Trifluoperazine/pharmacology , Zygomycosis/microbiology , Drug Synergism , Fungi/isolation & purification , Humans , Meningoencephalitis/microbiology , Microbial Sensitivity Tests , Rhinitis/microbiology
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