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3 Publications visible to you, out of a total of 3
Lactobacillus rhamnosus colonisation antagonizes Candida albicans by forcing metabolic adaptations that compromise pathogenicity.

Abstract (Expand)

Intestinal microbiota dysbiosis can initiate overgrowth of commensal Candida species - a major predisposing factor for disseminated candidiasis. Commensal bacteria such as Lactobacillus rhamnosus can … antagonize Candida albicans pathogenicity. Here, we investigate the interplay between C. albicans, L. rhamnosus, and intestinal epithelial cells by integrating transcriptional and metabolic profiling, and reverse genetics. Untargeted metabolomics and in silico modelling indicate that intestinal epithelial cells foster bacterial growth metabolically, leading to bacterial production of antivirulence compounds. In addition, bacterial growth modifies the metabolic environment, including removal of C. albicans' favoured nutrient sources. This is accompanied by transcriptional and metabolic changes in C. albicans, including altered expression of virulence-related genes. Our results indicate that intestinal colonization with bacteria can antagonize C. albicans by reshaping the metabolic environment, forcing metabolic adaptations that reduce fungal pathogenicity.

Authors: R. Alonso-Roman, A. Last, M. H. Mirhakkak, J. L. Sprague, L. Moller, P. Grossmann, K. Graf, R. Gratz, S. Mogavero, S. Vylkova, G. Panagiotou, S. Schauble, B. Hube, M. S. Gresnigt

Date Published: 9th Jun 2022

Publication Type: Journal

From environmental adaptation to host survival: Attributes that mediate pathogenicity of Candida auris.

Abstract (Expand)

Candida species are a major cause of invasive fungal infections. While Candida albicans, C. glabrata, C. parapsilosis, and C. tropicalis are the most dominant species causing life-threatening candidiasis, … C. auris recently emerged as a new species causing invasive infections with high rates of clinical treatment failures. To mimic initial phases of systemic Candida infections with dissemination via the bloodstream and to elucidate the pathogenic potential of C. auris, we used an ex vivo whole blood infection model. Similar to other clinically relevant Candida spp., C. auris is efficiently killed in human blood, but showed characteristic patterns of immune cell association, survival rates, and cytokine induction. Dual-species transcriptional profiling of C. auris-infected blood revealed a unique C. auris gene expression program during infection, while the host response proofed similar and conserved compared to other Candida species. C. auris-specific responses included adaptation and survival strategies, such as counteracting oxidative burst of immune cells, but also expression of potential virulence factors, (drug) transporters, and cell surface-associated genes. Despite comparable pathogenicity to other Candida species in our model, C. auris-specific transcriptional adaptations as well as its increased stress resistance and long-term environmental survival, likely contribute to the high risk of contamination and distribution in a nosocomial setting. Moreover, infections of neutrophils with pre-starved C. auris cells suggest that environmental preconditioning can have modulatory effects on the early host interaction. In summary, we present novel insights into C. auris pathogenicity, revealing adaptations to human blood and environmental niches distinctive from other Candida species.

Authors: S. Allert, D. Schulz, P. Kammer, P. Grossmann, T. Wolf, S. Schauble, G. Panagiotou, S. Brunke, B. Hube

Date Published: 10th Feb 2022

Publication Type: Journal

Lipid metabolic signatures deviate in sepsis survivors compared to non-survivors.

Abstract (Expand)

Sepsis remains a major cause of death despite advances in medical care. Metabolic deregulation is an important component of the survival process. Metabolomic analysis allows profiling of critical … metabolic functions with the potential to classify patient outcome. Our prospective longitudinal characterization of 33 septic and non-septic critically ill patients showed that deviations, independent of direction, in plasma levels of lipid metabolites were associated with sepsis mortality. We identified a coupling of metabolic signatures between liver and plasma of a rat sepsis model that allowed us to apply a human kinetic model of mitochondrial beta-oxidation to reveal differing enzyme concentrations for medium/short-chain hydroxyacyl-CoA dehydrogenase (elevated in survivors) and crotonase (elevated in non-survivors). These data suggest a need to monitor cellular energy metabolism beyond the available biomarkers. A loss of metabolic adaptation appears to be reflected by an inability to maintain cellular (fatty acid) metabolism within a "corridor of safety".

Authors: W. Khaliq, P. Grossmann, S. Neugebauer, A. Kleyman, R. Domizi, S. Calcinaro, D. Brealey, M. Graler, M. Kiehntopf, S. Schauble, M. Singer, G. Panagiotou, M. Bauer

Date Published: 11th Dec 2020

Publication Type: Not specified

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