Commensal gut microbes and their metabolites inhibit bacterial pathogen growth
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PROVIDER: PRJEB59984 | ENA |
REPOSITORIES: ENA
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Project description:The spread of multidrug-resistant (MDR) bacteria, such as the skin commensal Staphylococcus aureus, is a worldwide heath challenge; therefore, new methods to counteract the over-colonization and virulence of opportunistic pathogenic biotypes are highly urgent. We characterized and compared the activity of Lacticaseibacillus rhamnosus LR06 (DSM 21981) and Lactobacillus johnsonii LJO02 (DSM 33828) cell-free supernatants (CFSs), produced in a conventional animal-based MRS medium and in an innovative vegetal TIL, versus the MDR Staphylococcus aureus (ATCC 43300). CFSs were analysed via high-resolution mass spectrometry and gas-chromatography for short chain fatty acids (SCFAs), lactic acid and protein composition, while their activity was assessed towards i) the viability and metabolic activity of the MRSA strain through optical density and alamarBlue assay, and ii) the capability to inhibit/disaggregate the pathogenic biofilm, via crystal violet staining. All the CFSs reduce viable and metabolically active S. aureus, with the TIL medium more efficient, respect to MRS, in stimulating lactic acid bacteria metabolism and reducing the virulent biofilm. CFSs from LJO02 produced in TIL are the best, thanks to specific SCFAs and proteic metabolites. In conclusion, antagonistic non-pathogenic CFSs represent a promising and strategic approach, with potential applications as bacteriotherapy, and bioremediation of hospital equipments surfaces.
2022-06-09 | PXD030916 | Pride
Project description:The complex bacterial populations that constitute the gut microbiota can harbor antibiotic resistance genes (ARGs), including those encoding β-lactamase enzymes (BLA), which degrade commonly prescribed antibiotics such as ampicillin. The prevalence of such genes in commensal bacteria has been increased in recent years by the wide use of antibiotics in human populations and in livestock. While transfer of ARGs between bacterial species has well-established dramatic public health implications, these genes can also function in trans within bacterial consortia, where antibiotic-resistant bacteria can provide antibiotic-sensitive neighbors with leaky protection from drugs, as shown both in vitro and in vivo, in models of lung and subcutaneous coinfection. However, whether the expression of ARGs by harmless commensal bacterial species can destroy antibiotics in the intestinal lumen and shield antibiotic-sensitive pathogens is unknown. To address this question, we colonized germfree or wild-type mice with a model intestinal commensal strain of Escherichia coli that produces either functional or defective BLA. Mice were subsequently infected with Listeria monocytogenes or Clostridioides difficile, followed by treatment with oral ampicillin. The production of functional BLA by commensal E. coli markedly reduced clearance of these pathogens and enhanced systemic dissemination during ampicillin treatment. Pathogen resistance was independent of ARG acquisition via horizontal gene transfer but instead relied on antibiotic degradation in the intestinal lumen by BLA. We conclude that commensal bacteria that have acquired ARGs can mediate shielding of pathogens from the bactericidal effects of antibiotics.
| S-EPMC7093146 | biostudies-literature
Project description:Lichens are a source of secondary metabolites with significant pharmacological potential. Data regarding their possible application in glioblastoma (GBM) treatment are, however scarce. The study aimed to analyze the mechanism of action of six lichen secondary metabolites: atranorin, caperatic acid, physodic acid, squamatic acid, salazinic acid, and lecanoric acid using two- and three-dimensional GBM cell line models. The Parallel Artificial Membrane Permeation Assay was used to predict the blood-brain barrier penetration ability of the tested compounds. Their cytotoxicity was analyzed using MTT test on A-172, T98G, and U-138 MG cells. Flow cytometry was applied for the analysis of oxidative stress, cell cycle distribution, and apoptosis, whereas qPCR and microarrays detected the induced transcriptomic changes. Our data confirm the ability of lichen secondary metabolites to cross the blood-brain barrier and exert cytotoxicity against GBM cells. Moreover, the compounds generated oxidative stress, interfered with the cell cycle, and induced apoptosis in T98G cells. They also inhibited Wnt/β-catenin pathway, and this effect was even stronger in case of a co-treatment with temozolomide. Transcriptomic changes in cancer related genes induced by caperatic acid and temozolomide were the most pronounced. Lichen secondary metabolites, in particular caperatic acid should be further analyzed as potential anti-GBM agents.
2022-03-23 | GSE199185 | GEO
Project description:Intestinal bacterial metabolites are an important communication tool between the host immune system and the commensal microbiota to establish mutualism. In a recent paper published in Science, Wendy Garrett and her colleagues report an exciting role of the three most abundant microbial-derived short-chain fatty acids (SCFA), acetic acid, propionic acid and butyric acid, in colonic regulatory T cell (cTreg) homeostasis.
| S-EPMC3847568 | biostudies-other
Project description:Genetic and molecular evidence to support the hypothesis that fungal secondary metabolites play a significant role in protecting the fungi against fungivory is scarce. We investigated the impact of fungal secondary metabolites on transcript regulation of stress related expressed sequence tags (ESTs) of the Collembola Folsomia candida feeding on mixed vs. single diets. Aspergillus nidulans wildtype (WT; Ascomycota) able to produce secondary metabolites including sterigmatocystin (ST) and a knockout mutant with reduced secondary metabolism (A. nidulans ΔLaeA) were combined with the high quality fungus Cladosporium cladosporioides as mixed diets or offered as single diets. We hypothesized that (i) A. nidulans WT triggers more genes associated with stress responses compared to the A. nidulans ΔlaeA strain with suppressed secondary metabolism, (ii) C. cladosporioides causes significantly different transcript regulation than the A. nidulans strains ΔlaeA and WT, and (iii) mixed diets will cause significantly different transcript expression levels than single diets. All three hypotheses are generally supported despite the fact that many functions of the affected ESTs are unknown. The results bring molecular evidence for the existence of a link between fungal secondary metabolites and responses in springtails supporting the hypothesis that fungal secondary metabolites act as a shield against fungivory.
2010-02-03 | GSE19930 | GEO
Project description:Genetic and molecular evidence to support the hypothesis that fungal secondary metabolites play a significant role in protecting the fungi against fungivory is scarce. We investigated the impact of fungal secondary metabolites on transcript regulation of stress related expressed sequence tags (ESTs) of the Collembola Folsomia candida feeding on mixed vs. single diets. Aspergillus nidulans wildtype (WT; Ascomycota) able to produce secondary metabolites including sterigmatocystin (ST) and a knockout mutant with reduced secondary metabolism (A. nidulans ?LaeA) were combined with the high quality fungus Cladosporium cladosporioides as mixed diets or offered as single diets. We hypothesized that (i) A. nidulans WT triggers more genes associated with stress responses compared to the A. nidulans ?laeA strain with suppressed secondary metabolism, (ii) C. cladosporioides causes significantly different transcript regulation than the A. nidulans strains ?laeA and WT, and (iii) mixed diets will cause significantly different transcript expression levels than single diets. All three hypotheses are generally supported despite the fact that many functions of the affected ESTs are unknown. The results bring molecular evidence for the existence of a link between fungal secondary metabolites and responses in springtails supporting the hypothesis that fungal secondary metabolites act as a shield against fungivory. Twenty-three day old Folsomia candida were fed ad libitum for five days to fungal cuts respectively Cladosporium cladosporoides, Aspergillus nidulans WT, Aspergillus nidulans ?LaeA and two mixed diets of C.cladosporoides/A. nidulans WT (mix 1) and C. cladosporoides/A. nudlans ?LaeA (mix2) respectively. Four biological replicates were used for every treatment and a dye swap was used with the Cy3/Cy5 labels. This resulted in 20 samples which were analysed in 10 hybridisations executed in an interwoven loop design. The C. cladosporoides diet was used as the reference in the data analysis.
2010-02-02 | E-GEOD-19930 | biostudies-arrayexpress
Project description:While the structure and regulatory networks that govern type-six secretion system (T6SS) activity of Vibrio cholerae are becoming increasingly clear, we know less about the role of T6SS in disease. Under laboratory conditions, V. cholerae uses T6SS to outcompete many Gram-negative species, including other V. cholerae strains and human commensal bacteria. However, the role of these interactions has not been resolved in an in vivo setting. We used the Drosophila melanogaster model of cholera to define the contribution of T6SS to V. cholerae pathogenesis. Here, we demonstrate that interactions between T6SS and host commensals impact pathogenesis. Inactivation of T6SS, or removal of commensal bacteria, attenuates disease severity. Reintroduction of the commensal, Acetobacter pasteurianus, into a germ-free host is sufficient to restore T6SS-dependent pathogenesis in which T6SS and host immune responses regulate viability. Together, our data demonstrate that T6SS acts on commensal bacteria to promote the pathogenesis of V. cholerae.
| S-EPMC6142279 | biostudies-literature
Project description:Over the past decade, there has been increasing evidence highlighting the implication of the gut microbiota in a variety of brain disorders such as depression, anxiety, and schizophrenia. Studies have shown that depression affects the stability of gut microbiota, but the impact of antidepressant treatments on microbiota structure and metabolism remains underexplored. In this study, we investigated the in vitro antimicrobial activity of antidepressants from different therapeutic classes against representative strains of human gut microbiota. Six different antidepressants: phenelzine, venlafaxine, desipramine, bupropion, aripiprazole and (S)-citalopram have been tested for their antimicrobial activity against 12 commensal bacterial strains using agar well diffusion, microbroth dilution method, and colony counting. The data revealed an important antimicrobial activity (bacteriostatic or bactericidal) of different antidepressants against the tested strains, with desipramine and aripiprazole being the most inhibitory. Strains affiliating to most dominant phyla of human microbiota such as Akkermansia muciniphila, Bifidobacterium animalis and Bacteroides fragilis were significantly altered, with minimum inhibitory concentrations (MICs) ranged from 75 to 800 μg/mL. A significant reduction in bacterial viability was observed, reaching 5 logs cycle reductions with tested MICs ranged from 400 to 600 μg/mL. Our findings demonstrate that gut microbiota could be altered in response to antidepressant drugs.
| S-EPMC7578019 | biostudies-literature
Project description:The microbiome is an essential component of ecological systems and is comprised of a diverse array of microbes. Over the past decades, the accumulated observational evidence reveals a close correlation between the microbiome and human health and disease. Many groups are now manipulating individual microbial strains, species and the community as a whole to gain a mechanistic understanding of the functions of the microbiome. Here, we discuss three major approaches for introducing DNA to engineer model bacteria and isolated undomesticated bacteria, including transformation, transduction, and conjugation. We provide an overview of these approaches and describe the advantages and limitations of each method. In addition, we highlight examples of human microbiome engineering using these approaches. Finally, we provide perspectives for the future of microbiome engineering.
| S-EPMC11610962 | biostudies-literature
Project description:BackgroundOur current view of nature depicts a world where macroorganisms dwell in a landscape full of microbes. Some of these microbes not only transit but establish themselves in or on hosts. Although hosts might be occupied by microbes for most of their lives, a microbe-free stage during their prenatal development seems to be the rule for many hosts. The questions of who the first colonizers of a newborn host are and to what extent these are obtained from the parents follow naturally.ResultsWe have developed a mathematical model to study the effect of the transfer of microbes from parents to offspring. Even without selection, we observe that microbial inheritance is particularly effective in modifying the microbiome of hosts with a short lifespan or limited colonization from the environment, for example by favouring the acquisition of rare microbes.ConclusionBy modelling the inheritance of commensal microbes to newborns, our results suggest that, in an eco-evolutionary context, the impact of microbial inheritance is of particular importance for some specific life histories.
| S-EPMC9204957 | biostudies-literature