Your email was sent successfully. Check your inbox.

An error occurred while sending the email. Please try again.

Proceed reservation?

Export
  • 1
    In: Cell Host & Microbe, Elsevier BV, Vol. 30, No. 6 ( 2022-06), p. 824-835.e6
    Type of Medium: Online Resource
    ISSN: 1931-3128
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2022
    detail.hit.zdb_id: 2276339-9
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 2
    In: Applied and Environmental Microbiology, American Society for Microbiology, Vol. 85, No. 10 ( 2019-05-15)
    Abstract: A mechanistic understanding of microbe-host interactions is critical to developing therapeutic strategies for targeted modulation of the host immune system. Different members of the gut symbiont species Lactobacillus reuteri modulate host health by, for example, reduction of intestinal inflammation. Previously, it was shown that L. reuteri activates the aryl hydrocarbon receptor (AhR), a ligand-activated transcription factor that plays an important role in the mucosal immune system, by the production of tryptophan catabolites. Here, we identified a novel pathway by which L. reuteri activates AhR, which is independent of tryptophan metabolism. We screened a library of 36  L. reuteri strains and determined that R2lc and 2010, strains with a pigmented phenotype, are potent AhR activators. By whole-genome sequencing and comparative genomics, we identified genes unique to R2lc and 2010. Our analyses demonstrated that R2lc harbors two genetically distinct polyketide synthase (PKS) clusters, functionally unknown ( fun ) and pks , each carried by a multicopy plasmid. Inactivation of pks , but not fun , abolished the ability of R2lc to activate AhR. L. reuteri 2010 has a gene cluster homologous to the pks cluster in R2lc with an identical gene organization, which is also responsible for AhR activation. In conclusion, we identified a novel PKS pathway in L. reuteri R2lc and 2010 that is responsible for AhR activation. IMPORTANCE Temporary changes in the composition of the microbiota, for example, by oral administration of probiotics, can modulate the host immune system. However, the underlying mechanisms by which probiotics interact with the host are often unknown. Here, we show that Lactobacillus reuteri R2lc and 2010 harbor an orthologous PKS gene cluster that activates the aryl hydrocarbon receptor (AhR). AhR is a ligand-activated transcription factor that plays a key role in a variety of diseases, including amelioration of intestinal inflammation. Understanding the mechanism by which a bacterium modulates the immune system is critical for applying rational selection strategies for probiotic supplementation. Finally, heterologous and/or optimized expression of PKS is a logical next step toward the development of next-generation probiotics to prevent and treat disease.
    Type of Medium: Online Resource
    ISSN: 0099-2240 , 1098-5336
    RVK:
    Language: English
    Publisher: American Society for Microbiology
    Publication Date: 2019
    detail.hit.zdb_id: 223011-2
    detail.hit.zdb_id: 1478346-0
    SSG: 12
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 3
    In: Nature Chemical Biology, Springer Science and Business Media LLC, Vol. 11, No. 9 ( 2015-9), p. 625-631
    Type of Medium: Online Resource
    ISSN: 1552-4450 , 1552-4469
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2015
    detail.hit.zdb_id: 2190276-8
    SSG: 12
    SSG: 15,3
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 4
    In: Circulation, Ovid Technologies (Wolters Kluwer Health), Vol. 144, No. Suppl_1 ( 2021-11-16)
    Abstract: Background: Staphylococcus aureus prosthetic valve endocarditis (PVE) is resistant to antimicrobial therapy and commonly associated with tissue invasion, which necessitates complex high risk surgical intervention for cure. Hypothesis: S. aureus virulence in infective endocarditis (IE) is dynamic and changes upon colonizing cardiac valves from blood stream. Methods: Six patients undergoing cardiac surgery for left-sided S. aureus IE, 3 native (NVE) and 3 PVE, were included in this study. Vegetation samples were collected during surgery as well as corresponding blood culture isolates during S. aureus bacteremia. Total RNA was extracted from all samples and underwent mRNA sequencing for transcriptomic analysis of S. aureus . Data was pooled into STAR aligner and gene expression related to virulence factors was compared between different groups (Deseq2; p-value 〈 0.05 for statistical significance). Results: In NVE vegetations, S. aureus showed an increased expression of genes associated with biofilm formation, cell division, and metabolic activity, when compared to blood culture isolates (e.g. rsmA , agrB , dnaK , clpB , ezrA , fusA , ftsZ , adh , pstS , qoxA ). S. aureus isolated from blood cultures had significantly higher expression of clfA (encoding for clumping factor A) compared to cardiac vegetations. Interestingly, in PVE vegetations, S. aureus had a significant higher expression of aur (encoding for metalloprotease aureolysin) compared to corresponding blood culture isolates or NVE vegetations. Aureolysin is an important virulence factor responsible for immune evasion and toxin production. Conclusions: In clinical IE, S. aureus up-regulates genes responsible for biofilm formation when attached to cardiac valves. Planktonic S. aureus cells in the blood stream express clfA , which could bind to fibrinogen to clump within platelet network to form vegetations. On prosthetic valves, S. aureus expresses aureolysin, which could function to evade the host immune response and promote destruction of cardiac tissues. These novel in-vivo findings provide explanations for S. aureus IE pathophysiology that warrant further investigation.
    Type of Medium: Online Resource
    ISSN: 0009-7322 , 1524-4539
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2021
    detail.hit.zdb_id: 1466401-X
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 5
    Online Resource
    Online Resource
    American Association for Cancer Research (AACR) ; 2023
    In:  Cancer Research Vol. 83, No. 7_Supplement ( 2023-04-04), p. 4243-4243
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 83, No. 7_Supplement ( 2023-04-04), p. 4243-4243
    Abstract: Background: A diet rich in colorful fruits and vegetables is effective for the prevention of various inflammation-induced cancer types. Mechanistically, this effect has been attributed to the potent antioxidant properties of flavonoid molecules. However, contrary to observations in mice, the success of flavonoids in human dietary cancer prevention trials is often dampened due to large interpersonal variation. Antioxidant activity alone does not explain this variability, suggesting there is an additional important variable that has not been accounted for. Since flavonoids have a poor bioavailability and predominantly passage into the large intestine, we hypothesize that gut microbial metabolism is essential for flavonoid bioactivity in colon cancer prevention. Goals and Objectives: The goal of this study was to evaluate the impact of microbiota composition on the efficacy of dietary flavonoids in preventing intestinal tumorigenesis. Methods: We used the adenomatous polyposis coli - multiple intestinal neoplasia (ApcMin/+) mouse model, which is genetically predisposed to develop adenomas along its gastrointestinal tract. Development of these adenomas and eventual adenocarcinoma formation is further influenced by factors such as inflammation, dietary input and the gut microbiota. Animals were fed a control high fat diet (HFD) or prevention diets consisting of 1% berry extract, 1% purified flavonoid or 1% microbial catabolite, all on the HFD background. The contribution of the microbiota was modelled by including experimental groups that received an antibiotic cocktail in their drinking water throughout the course of the experiment. For these animals, microbiota community composition was determined by 16S rRNA sequencing, plasma was collected for histological profiling and metabolomics analysis and end-point measurements of intestinal tumor numbers and size were performed. Results: Supplementation with berry extract significantly reduced colon tumor numbers and incidence in male, but not in female mice. This effect was negated in mice on antibiotic drinking water, implicating the involvement of the gut microbiota. Community analysis revealed a relative increase in Erysipelotrichaceae, Clostridia and Akkermansia in the berry supplemented versus HFD control mice. In addition, their systemic monocyte counts were reduced. Dietary supplementation with a major gut microbial flavonoid catabolite, did not reduce colon tumor formation, suggesting the functional involvement of different microbial metabolites. Conclusions: Our study demonstrates the involvement of the mouse gut microbiota in dietary prevention of colon tumor formation. These effects impact circulating monocytes and are linked to changes in the plasma metabolome. We are currently elucidating the microbial actors and associated molecular pathways involved. Citation Format: Beckey DeLucia, Jan Claesen. Dietary flavonoids prevent colon tumor formation in ApcMin/+ mice in a microbiome- and sex-dependent manner. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 4243.
    Type of Medium: Online Resource
    ISSN: 1538-7445
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2023
    detail.hit.zdb_id: 2036785-5
    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 6
    In: Nature Microbiology, Springer Science and Business Media LLC, Vol. 4, No. 12 ( 2019-10-21), p. 2393-2404
    Type of Medium: Online Resource
    ISSN: 2058-5276
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2019
    detail.hit.zdb_id: 2845610-5
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 7
    In: Expert Review of Medical Devices, Informa UK Limited, Vol. 18, No. 1 ( 2021-01-02), p. 47-62
    Type of Medium: Online Resource
    ISSN: 1743-4440 , 1745-2422
    Language: English
    Publisher: Informa UK Limited
    Publication Date: 2021
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 8
    In: Microbiology Spectrum, American Society for Microbiology, Vol. 9, No. 3 ( 2021-12-22)
    Abstract: Cerebrospinal fluid (CSF) circulating in the human central nervous system has long been considered aseptic in healthy individuals, because normally, the blood-brain barrier can protect against microbial invasions. However, this dogma has been called into question by several reports that microbes were identified in human brains, raising the question of whether there is a microbial community in the CSF of healthy individuals without neurological diseases. Here, we collected CSF samples and other samples, including one-to-one matched oral and skin swab samples (positive controls), from 23 pregnant women aged between 23 and 40 years. Normal saline samples (negative controls), sterile swabs, and extraction buffer samples (contamination controls) were also collected. Twelve of the CSF specimens were also used to evaluate the physiological activities of detected microbes. Metagenomic and metatranscriptomic sequencing was performed in these 116 specimens. A total of 620 nonredundant microbes were detected, which were dominated by bacteria (74.6%) and viruses (24.2%), while in CSF samples, metagenomic sequencing found only 26 nonredundant microbes, including one eukaryote, four bacteria, and 21 viruses (mostly bacteriophages). The beta diversity of microbes compared between CSF metagenomic samples and other types of samples (except negative controls) was significantly different from that of the CSF self-comparison. In addition, there was no active or viable microbe in the matched metagenomic and metatranscriptomic sequencing of CSF specimens after subtracting those also found in normal saline, DNA extraction buffer, and skin swab specimens. In conclusion, our results showed no strong evidence of a colonized microbial community present in the CSF of healthy individuals. IMPORTANCE The microbiome is prevalent throughout human bodies, with profound health implications. However, it remains unclear whether it is present and active in human CSF, which has been long considered aseptic due to the blood-brain barrier. Here, we applied unbiased metagenomic and metatranscriptomic sequencing to detect the presence of a microbiome in CSF collected from 23 pregnant women with matched controls. Analysis of 116 specimens found no strong evidence to support the presence of a colonized microbiome in CSF. Our findings will strengthen our understanding of the internal environment of the CSF in healthy people, which has strong implications for human health, especially for neurological infections and disorders, and will help further disease diagnostics, prevention, and therapeutics in clinical settings.
    Type of Medium: Online Resource
    ISSN: 2165-0497
    Language: English
    Publisher: American Society for Microbiology
    Publication Date: 2021
    detail.hit.zdb_id: 2807133-5
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 9
    In: Microbiology Spectrum, American Society for Microbiology, Vol. 10, No. 3 ( 2022-06-29)
    Abstract: The capacity of the human microbiome to modulate inflammation in the context of cancer is becoming increasingly clear. Myeloproliferative neoplasms (MPNs) are chronic hematologic malignancies in which inflammation plays a key role in disease initiation, progression, and symptomatology. To better understand the composition of the gut microbiome in patients with MPN, triplicate fecal samples were collected from 25 MPN patients and 25 non-MPN controls. Although most of the variance between the microbial community compositions could be attributed to the individual (permutational analysis of variance [PERMANOVA], R 2  = 0.92, P  = 0.001), 1.7% of the variance could be attributed to disease status (MPN versus non-MPN). When a more detailed analysis was performed, significantly fewer reads mapping to a species of Phascolarctobacterium , a microbe previously associated with reduced inflammation, were found in MPNs. Further, our data revealed an association between Parabacteroides and tumor necrosis factor alpha (TNF-α), an inflammatory cytokine elevated in MPNs. Taken together, our results indicate a significant difference in the microbiome of MPN patients compared to non-MPN controls, and we identify specific species which may have a role in the chronic inflammation central to this disease. IMPORTANCE MPNs are chronic blood cancers in which inflammation plays a key role in disease initiation, progression, and symptomatology. The gut microbiome modulates normal blood development and inflammation and may also impact the development and manifestation of blood cancers. Therefore, the microbiome may be an important modulator of inflammation in MPN and could potentially be leveraged therapeutically in this disease. However, the relationship between the gut microbiome and MPNs has not been defined. Therefore, we performed an evaluation of the MPN microbiome, comparing the microbiomes of MPN patients with healthy donors and between MPN patients with various states of disease.
    Type of Medium: Online Resource
    ISSN: 2165-0497
    Language: English
    Publisher: American Society for Microbiology
    Publication Date: 2022
    detail.hit.zdb_id: 2807133-5
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 10
    In: Microbiology Spectrum, American Society for Microbiology, Vol. 10, No. 6 ( 2022-12-21)
    Abstract: Social hygiene is seriously threatened by the rise in colistin (COL) resistance against Gram-negative bacteria (GNB). With resistance to last-line antibiotics such as COL becoming more common, it is imperative to identify alternative treatment options. In our work, we sought to determine if COL plus kaempferol (KP) present synergistic effects on the antibacterial and antibiofilm activities against colistin-resistant (Col-R) GNB in vivo and in vitro . Twenty-four Col-R GNB were collected as the experimental strains. The synergistic activity of COL and KP was evaluated by checkerboard method, time-killing assays, and the Galleria mellonella experiment. The antibiofilm effectiveness of the COL/KP combination against Col-R GNB was assessed using biofilm inhibition and eradication assays and scanning electron microscopy (SEM). Cytotoxicity tests were performed to detect the toxicity of KP monotherapy or combination therapy. There is synergistic antibacterial activity of COL and KP combination in vitro . KP combined with COL could inhibit the formation of bacterial biofilms. The amalgamation of COL and KP considerably reduced the amount of bacteria in the biofilm, according to the SEM findings. The COL/KP combination improved the survivorship of infected larvae in the G. mellonella in vivo infection model. In addition, the combination of KP and COL showed no cytotoxicity at synergistic combined concentrations according to cytotoxicity assays. This represents the first account of the antibacterial and antibiofilm activities of KP in combination with COL against Col-R GNB. Therefore, our results may provide an effective alternative route to combat Col-R GNB infections. IMPORTANCE COL is one of the few antibiotics effective against clinical isolates of GNB. However, in recent years, GNB resistance to colistin has been increasing. As a result, the combined application of colistin in conjunction with nonantibacterial medications has garnered considerable interest. In this work, the KP/COL combination showed effective antibacterial and antibiofilm activities in vitro and in vivo . The synergistic effect of combined application may be attributed to membrane permeability. Due to the low cytotoxicity of the combined concentration, the combination exhibits a promising future for use in clinical anti-infection treatments. This finding might broaden the potential applications for COL.
    Type of Medium: Online Resource
    ISSN: 2165-0497
    Language: English
    Publisher: American Society for Microbiology
    Publication Date: 2022
    detail.hit.zdb_id: 2807133-5
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
Close ⊗
This website uses cookies and the analysis tool Matomo. Further information can be found on the KOBV privacy pages