Novel role of a family of major facilitator transporters in biofilm development and virulence of Candida albicans

QDR proteins of C. albicans do not carry out their conserved transport function, rather they affect the pathogenesis of the organism and their deletion mutants also show architectural defects in biofilms and massive remodelling of lipids as a compensatory mechanism to sustain their loss.

Download Full-text

Let-7e-5p Regulates GLP-1 Content and Basal Release From Enteroendocrine L Cells From DIO Male Mice

Endocrinology ◽

10.1210/endocr/bqz037 ◽

2019 ◽

Vol 161 (2) ◽

Author(s):

Sandra Handgraaf ◽

Rodolphe Dusaulcy ◽

Florian Visentin ◽

Jacques Philippe ◽

Yvan Gosmain

Keyword(s):

Compensatory Mechanism ◽

L Cells ◽

Low Fat Diet ◽

Obesity And Diabetes ◽

Basal Release ◽

Glucagon Like Peptide 1 ◽

Cell Transcriptome ◽

Microarray Analyses

Abstract Characterization of enteroendocrine L cells in diabetes is critical for better understanding of the role of glucagon-like peptide-1 (GLP-1) in physiology and diabetes. We studied L-cell transcriptome changes including microRNA (miRNA) dysregulation in obesity and diabetes. We evaluated the regulation of miRNAs through microarray analyses on sorted enteroendocrine L cells from control and obese glucose-intolerant (I-HFD) and hyperglycemic (H-HFD) mice after 16 weeks of respectively low-fat diet (LFD) or high-fat diet (HFD) feeding. The identified altered miRNAs were studied in vitro using the mouse GLUTag cell line to investigate their regulation and potential biological functions. We identified that let-7e-5p, miR-126a-3p, and miR-125a-5p were differentially regulated in L cells of obese HFD mice compared with control LFD mice. While downregulation of let-7e-5p expression was observed in both I-HFD and H-HFD mice, levels of miR-126a-3p increased and of miR-125a-5p decreased significantly only in I-HFD mice compared with controls. Using miRNA inhibitors and mimics we observed that modulation of let-7e-5p expression affected specifically GLP-1 cellular content and basal release, whereas Gcg gene expression and acute GLP-1 secretion and cell proliferation were not affected. In addition, palmitate treatment resulted in a decrease of let-7e-5p expression along with an increase in GLP-1 content and release, suggesting that palmitate acts on GLP-1 through let-7e-5p. By contrast, modulation of miR-125a-5p and miR-126a-3p in the same conditions did not affect content or secretion of GLP-1. We conclude that decrease of let-7e-5p expression in response to palmitate may constitute a compensatory mechanism contributing to maintaining constant glycemia in obese mice.

Download Full-text

Gut microbiota profiles and characterization of cultivable fungal isolates in IBS patients

Applied Microbiology and Biotechnology ◽

10.1007/s00253-021-11264-4 ◽

2021 ◽

Author(s):

Piero Sciavilla ◽

Francesco Strati ◽

Monica Di Paola ◽

Monica Modesto ◽

Francesco Vitali ◽

...

Keyword(s):

Candida Albicans ◽

Gut Microbiota ◽

Healthy Subjects ◽

Fungal Isolates ◽

Key Points ◽

Health Promoting ◽

Irritable Bowel

Abstract Studies so far conducted on irritable bowel syndrome (IBS) have been focused mainly on the role of gut bacterial dysbiosis in modulating the intestinal permeability, inflammation, and motility, with consequences on the quality of life. Limited evidences showed a potential involvement of gut fungal communities. Here, the gut bacterial and fungal microbiota of a cohort of IBS patients have been characterized and compared with that of healthy subjects (HS). The IBS microbial community structure differed significantly compared to HS. In particular, we observed an enrichment of bacterial taxa involved in gut inflammation, such as Enterobacteriaceae, Streptococcus, Fusobacteria, Gemella, and Rothia, as well as depletion of health-promoting bacterial genera, such as Roseburia and Faecalibacterium. Gut microbial profiles in IBS patients differed also in accordance with constipation. Sequence analysis of the gut mycobiota showed enrichment of Saccharomycetes in IBS. Culturomics analysis of fungal isolates from feces showed enrichment of Candida spp. displaying from IBS a clonal expansion and a distinct genotypic profiles and different phenotypical features when compared to HS of Candida albicans isolates. Alongside the well-characterized gut bacterial dysbiosis in IBS, this study shed light on a yet poorly explored fungal component of the intestinal ecosystem, the gut mycobiota. Our results showed a differential fungal community in IBS compared to HS, suggesting potential for new insights on the involvement of the gut mycobiota in IBS. Key points • Comparison of gut microbiota and mycobiota between IBS and healthy subjects • Investigation of cultivable fungi in IBS and healthy subjects • Candida albicans isolates result more virulent in IBS subjects compared to healthy subjects

Download Full-text

The role of PKMζ in the maintenance of long-term memory: a review

Reviews in the Neurosciences ◽

10.1515/revneuro-2020-0105 ◽

2021 ◽

Vol 0 (0) ◽

Author(s):

Hamish Patel ◽

Reza Zamani

Keyword(s):

Protein Kinase C ◽

Protein Kinase ◽

Long Term Potentiation ◽

Global Memory ◽

Long Term Memory ◽

Compensatory Mechanism ◽

Term Memory ◽

Kinase C

Abstract Long-term memories are thought to be stored in neurones and synapses that undergo physical changes, such as long-term potentiation (LTP), and these changes can be maintained for long periods of time. A candidate enzyme for the maintenance of LTP is protein kinase M zeta (PKMζ), a constitutively active protein kinase C isoform that is elevated during LTP and long-term memory maintenance. This paper reviews the evidence and controversies surrounding the role of PKMζ in the maintenance of long-term memory. PKMζ maintains synaptic potentiation by preventing AMPA receptor endocytosis and promoting stabilisation of dendritic spine growth. Inhibition of PKMζ, with zeta-inhibitory peptide (ZIP), can reverse LTP and impair established long-term memories. However, a deficit of memory retrieval cannot be ruled out. Furthermore, ZIP, and in high enough doses the control peptide scrambled ZIP, was recently shown to be neurotoxic, which may explain some of the effects of ZIP on memory impairment. PKMζ knockout mice show normal learning and memory. However, this is likely due to compensation by protein-kinase C iota/lambda (PKCι/λ), which is normally responsible for induction of LTP. It is not clear how, or if, this compensatory mechanism is activated under normal conditions. Future research should utilise inducible PKMζ knockdown in adult rodents to investigate whether PKMζ maintains memory in specific parts of the brain, or if it represents a global memory maintenance molecule. These insights may inform future therapeutic targets for disorders of memory loss.

Download Full-text

The role of annexin A1 in Candida albicans and Candida auris infections in murine neutrophils

Microbial Pathogenesis ◽

10.1016/j.micpath.2020.104689 ◽

2021 ◽

Vol 150 ◽

pp. 104689

Author(s):

José Marcos Sanches ◽

Luana Rossato ◽

Izabella Lice ◽

Anna Maria Alves de Piloto Fernandes ◽

Gustavo Henrique Bueno Duarte ◽

...

Keyword(s):

Candida Albicans ◽

Annexin A1 ◽

Candida Auris

Download Full-text

The Role of Exopolysaccharides in Oral Biofilms

Journal of Dental Research ◽

10.1177/0022034519845001 ◽

2019 ◽

Vol 98 (7) ◽

pp. 739-745 ◽

Cited By ~ 7

Author(s):

C. Cugini ◽

M. Shanmugam ◽

N. Landge ◽

N. Ramasubbu

Keyword(s):

Biofilm Formation ◽

Bacterial Colonization ◽

Super Resolution ◽

Extracellular Proteins ◽

Extracellular Polysaccharides ◽

Oral Biofilms ◽

The Matrix ◽

Oral Microbes ◽

Biofilm Development

The oral cavity contains a rich consortium of exopolysaccharide-producing microbes. These extracellular polysaccharides comprise a major component of the oral biofilm. Together with extracellular proteins, DNA, and lipids, they form the biofilm matrix, which contributes to bacterial colonization, biofilm formation and maintenance, and pathogenesis. While a number of oral microbes have been studied in detail with regard to biofilm formation and pathogenesis, the exopolysaccharides have been well characterized for only select organisms, namely Streptococcus mutans and Aggregatibacter actinomycetemcomitans. Studies on the exopolysaccharides of other oral organisms, however, are in their infancy. In this review, we present the current research on exopolysaccharides of oral microbes regarding their biosynthesis, regulation, contributions to biofilm formation and stability of the matrix, and immune evasion. In addition, insight into the role of exopolysaccharides in biofilms is highlighted through the evaluation of emerging techniques such as pH probing of biofilm colonies, solid-state nuclear magnetic resonance for macromolecular interactions within biofilms, and super-resolution microscopy analysis of biofilm development. Finally, exopolysaccharide as a potential nutrient source for species within a biofilm is discussed.

Download Full-text