Exopolysaccharides (EPS) are carbohydrate polymers produced by various bacteria, including species of the genus Lactobacillus. Until now, the link between the functional properties of these bacteria and their EPS remains poorly understood. Lactobacilli are used in a wide range of applications due to their protective effects against inflammation and their role in maintaining intestinal homeostasis. However, the functional properties of their EPS remain weakly characterized. This study investigated the EPS produced by Lactobacillus gasseri (Lg-EPS), a human-derived probiotic, focusing on their immunomodulatory activity and inhibitory effects on the growth and virulence of Candida albicans, an opportunistic fungal pathogen associated with dysbiosis and immune dysfunction. The results show that Lg-EPS are composed of 59.1% glucose, 26.0% galactose, 14.6% rhamnose, and 0.3% N-acetyl-glucosamine. Functionally, Lg-EPS reduced the expression of pro-inflammatory cytokines (IL-6, IL-8, CCL-2) and IL-6 protein levels, while increasing IL-10 expression and secretion. These effects were associated with downregulation of TLRs, MyD88 and NF-κB, alongside upregulation of the aryl hydrocarbon receptor (AhR), an intracellular transcription factor involved in immune modulation. Additionally, Lg-EPS increase induction of AhR activity in HT29-Lucia™ AhR cells. Furthermore, Lg-EPS inhibited C. albicans biofilm formation and fungal growth. These findings suggest that Lg-EPS contribute to immune regulation and antifungal defense via AhR activation. This receptor, known for sensing microbial metabolites, mediates anti-inflammatory effects by suppressing NF-κB signaling, enhancing IL-10 production, and reinforcing epithelial barrier function. This is the first report to demonstrate the AhR-dependent anti-inflammatory effect of bacterial EPS.

This study explores the adaptation of organic acid-based deep eutectic solvents (OA-DESs) as effective antimicrobial agents. Having already demonstrated their efficacy against planktonic bacteria in our previous research, herein we investigate their impact on more complex microbial forms, including biofilms, persister cells, and fungi (both human pathogenic and phytopathogenic). Our experiments revealed that OA-DESs effectively eradicated methicillin-resistant Staphylococcus aureus (MRSA) and Escherichia coli in the biofilms, inducing significant morphological changes. A three-log-unit reduction was observed for most OA-DESs at concentrations below 1% (v/v), a remarkable achievement for this class of materials. Additionally, with only one exception, OA-DESs did not promote persister cells formation, underscoring their potential for complete eradication of biofilm-enveloped bacteria. In another part of our study, OA-DESs were compared to conventional DESs against Candida albicans, Candida auris, and Aspergillus fumigatus. Results showed that while individual DES components exhibited minimal activity, their combination effectively inhibited fungal growth and induced substantial morphological changes. Lastly, OA-DESs were tested against the phytopathogens Zymoseptoria tritici and Venturia inaequalis. Though their activity was less pronounced compared to pathogenic strains, most OA-DESs inhibited the growth of both fungi at the highest tested concentrations. Despite the broad scope of this investigation, we believe this work provides valuable insights into the potential of DESs as antimicrobial agents, offering a strong foundation for future research and innovation in this field.

Worldwide, invasive candidiasis are a burden for the health system due to difficulties to manage patients, to the increasing of the resistance of the current therapeutics and the emergence of naturally resistant species of Candida. In this context, the development of innovative antifungal drugs is urgently needed. During invasive candidiasis, yeast is submitted to many stresses (oxidative, thermic, osmotic) in the human host. In order to resist in this context, yeast develops different strategy, especially the biosynthesis of trehalose. Starting from the 3D structural data of TPS2, an enzyme implicated in trehalose biosynthesis, we identified hydrazone as an interesting scaffold to design new antifungal drugs. Interestingly, our hydrazone derivatives which demonstrate antifungal and anti-biofilm effects on Candida spp., are non-toxic in in vitro and in vivo models (Galleria mellonella).

High-resolution mass spectrometry (HRMS) was coupled with ultra-high-performance liquid chromatography (UHPLC) to simultaneously quantify trehalose and trehalose 6-phosphate without derivatization or sample preparation. The use of full scan mode and exact mass analysis also makes it possible to carry out metabolomic analyses as well as semi-quantification. In addition, the use of different clusters in negative mode makes it possible to compensate for deficiencies in linearity and inerrant saturation at time-of-flight detectors. The method has been approved and validated for different matrices, yeasts, and bacteria, and has shown differentiation between bacteria as a function of growth temperatures.

The molecular composition and structural organization of the cell wall of filamentous fungi underlie the ability of the host to identify them as pathogens. Although the organization of the fungal cell wall, composed of 90% polysaccharides, is similar from one fungus to another, small variations condition their ability to trigger pattern recognition receptors. Because the incidence of mucormycosis, an emerging life-threatening infection caused by the species of the order Mucorales is increasing worldwide, the precise composition of the cell wall of two strains of Lichtheimia corymbifera was investigated in the early growth stages of germination (spores and germ-tubes) using trimethylsilylation and confocal microscopy. This study also characterizes the response of THP-1 cells to Mucorales. The study identified the presence of uncommon monosaccharides (fucose, galactose, and glucuronic acid) whose respective proportions vary according to the germination stage, revealing early parietal reorganization. Immunofluorescence studies confirmed the exposure of β-glucan on the surface of swollen spores and germ-tubes. Both spores and germ-tubes of L. corymbifera promoted an early and strong pro-inflammatory response, through TLR-2. Our results show the singularity of the cell wall of the order Mucorales, opening perspectives for the development of specific diagnostic biomarkers.

Background Intestinal fibrosis is a frequent complication of Crohn’s disease. However, the factors that cause chronicity and promote fibrogenesis are not yet understood. Aims In the present study, we evaluated the profibrotic effects of adherent-invasive Escherichia coli (AIEC) LF82 strain and Candida albicans in the gut. Methods Colonic fibrosis was induced in C57BL/6 mice by administration of three cycles of 2.5% (w/v) dextran sulfate sodium (DSS) for 5 weeks. LF82 and C. albicans were administered orally once at the start of each week or each cycle, respectively. Expression of markers of myofibroblast activation was determined in TGF-β1-stimulated human intestinal epithelial cells (IECs). Results LF82 administration exacerbated fibrosis in DSS-treated mice, revealed by increased colonic collagen deposition and expression of the profibrotic genes Col1a1 , Col3a1 , Fn1 and Vim . This was accompanied by enhanced gene expression of proinflammatory cytokines and chemokines, as well as more recruited inflammatory cells into the intestine. LF82 also potentiated TGF-β1-stimulated epithelial–mesenchymal transition and myofibroblast activation in IECs, by further inducing gene expression of the main mesenchymal cell markers FN1 and VIM and downregulating the IEC marker OCLN . Proinflammatory cytokines were overexpressed with LF82 in TGF-β1-stimulated IECs. Conversely, C. albicans did not affect intestinal fibrosis progression in DSS-treated mice or myofibroblast activation in TGF-β1-stimulated IECs. Conclusions These results demonstrate that AIEC strain LF82, but not C. albicans , may play a major profibrogenic role in the gut.

Alterations to the gut microbiota can cause an amplification of the inflammatory response to intestinal pathogens. We assessed the effect of Bacteroides thetaiotaomicron and Lactobacillus johnsonii on the elimination of Candida species and whether restoration of these two anaerobic bacteria could attenuate the development of colitis in mice. In this study, L. johnsonii and B. thetaiotaomicron interacted directly with Candida species and induced a degradation of the fungal cell wall, mediated via chitinase-like and mannosidase-like activities, which promoted the inhibition of Candida species growth. In the DSS-induced colitis model, oral administration of L. johnsonii and B. thetaiotaomicron to mice reduced the overgrowth of Escherichia coli, Enterococcus faecalis and Candida glabrata populations and resulted in a significant reduction in inflammatory parameters. L. johnsonii and B. thetaiotaomicron decreased pro-inflammatory mediators and enhanced the anti-inflammatory cytokine response with high TLR9 expression and chitinase-like protein-1 activation, which promoted the elimination of C. glabrata from the gut. Overall, these findings provide evidence that L. johnsonii and B. thetaiotaomicron decrease the development of colitis mediated by TLR9 and promote the elimination of C. glabrata from the gut via chitinase-like and mannosidase-like activities.

Platelets play an important role in the innate immune response. During candidaemia, circulating fungal polysaccharides, including chitin, are released into the bloodstream and can interact with platelets and induce modulation of platelet activities. However, the role of circulating chitin in platelet modulation has not been investigated. The aims of the present study were to assess the effect of fungal chitin on activation, adhesion, aggregation and receptor expression of platelets and their impact on the host defense against Candida albicans. Platelets pre-treated with different concentrations of chitin (10–400 μg/mL) extracted from C. albicans were analyzed in terms of activation, Toll-like receptor (TLR) expression, aggregation and adhesion to C. albicans. Chitin treatment reduced platelet adhesion to C. albicans and neutrophils. P-selectin expression was significantly decreased in platelets challenged with chitin. Aggregation and intracellular Ca2+ influx were also decreased in platelets. TLR8 mRNA and proteins were expressed in platelets pre-treated with chitin when compared to untreated platelets. Overall, chitin purified from C. albicans reduced the adhesion, activation and aggregation of platelets mediated via TLR8 stimulation by decreasing intracellular Ca2+ influx and P-selectin expression.

Resistance of the opportunistic pathogen Candida albicans to antifungal drugs has increased significantly in recent years. After screening 55 potential antifungal compounds from a chemical library, 2,3-dihydroxy-4-methoxybenzaldehyde (DHMB) was identified as having potential antifungal activity. The properties of DHMB were then assessed in vitro and in vivo against C. albicans overgrowth and intestinal inflammation. Substitution on the aromatic ring of DHMB led to a strong decrease in its biological activity against C. albicans. The MIC of DHMB was highly effective at eliminating C. albicans when compared to that of caspofungin or fluconazole. Additionally, DHMB was also effective against clinically isolated fluconazole- or caspofungin-resistant C. albicans strains. DHMB was administered to animals at high doses. This compound was not cytotoxic and was well-tolerated. In experimental dextran sodium sulphate (DSS)-induced colitis in mice, DHMB reduced the clinical and histological score of inflammation and promoted the elimination of C. albicans from the gut. This finding was supported by a decrease in aerobic bacteria while anaerobic bacteria populations were re-established in mice treated with DHMB. DHMB is a small organic molecule with antifungal properties and anti-inflammatory activity by exerting protective effects on intestinal epithelial cells.

The intestinal microbiota plays a crucial role in the maintenance of gut homeostasis. Changes in crosstalk between the intestinal epithelial cells, immune cells and the microbiota are critically involved in the development of inflammatory bowel disease. In the experimental mouse model, the development of colitis induced by dextran sulfate sodium (DSS) promotes overgrowth of the opportunistic yeast pathogen Candida glabrata. Conversely, fungal colonization aggravates inflammatory parameters. In the present study, we explored the effect of C. glabrata colonization on the diversity of the gut microbiota in a DSS-induced colitis model, and determined the impact of soluble β-glucans on C. glabrata-host interactions.