ABSTRACT: EMG produced TPA metagenomics assembly of PRJNA777294 data set (Tracking Genomic Characteristics across Oceanic Provinces: Contrasting Early and Mature Plastic Biofilm Communities).
Project description:Aspergillus fumigatus is a filamentous fungus found in compost and soil that can cause invasive and/or chronic disease in a broad spectrum of individuals. Diagnosis and aspergillosis treatment often occur during late stages of infection when A. fumigatus has formed dense networks of hyphae within the lung. These dense hyphal networks have hallmark characteristics of a microbial biofilm, a fungal mode of growth that can be recapitulated in vitro using a static, submerged biofilm culture model. A. fumigatus biofilms in this model are multicellular, encased in a thick ECM layer, and have reduced susceptibility to contemporary antifungal drugs. This reduced susceptibility is hypothesized to be in part due to spatial cellular quiescence in the biofilm that likely occurs in response to regions of low oxygen that form during biofilm development. The mechanisms underlying filamentous fungal cell physiology at different stages of biofilm development remain to be defined. Here, we utilized an RNA sequencing approach to evaluate changes in transcripts during A. fumigatus biofilm development. These analyses revealed an increase in transcripts associated with fermentation and a concomitant decrease in oxidative phosphorylation related transcripts. Further studies revealed that ethanol fermentation is important for mature biofilm biomass maintenance. Correspondingly, a gene predicted to be involved in mitigating ethanol mediated membrane stress was observed to also be required for mature biofilm biomass maintenance. Taken together, these data suggest changes in A. fumigatus carbon utilization as biofilms develop impact the ability to maintain a fully mature biofilm.
Project description:Photosensitizers (PS)s with aggregation-induced emission (AIE) properties have gained popularity in treating bacterial infections. However, most AIE PSs have poor water solubility and low selectivity, which greatly limit their applications in biological systems. Herein, we report a water-soluble and bacteria-targeting AIE PS, TPA-1, which showed minimum cytotoxicity towards human cells with and without light irradiation. Without light irradiation, TPA-1 acts as a narrow-spectrum antibacterial agent, eradicating planktonic S. aureus and inhibiting their biofilm formation. The mechanism study showed that TPA-1 targets S. aureus membrane, inhibits the supercoiling activity of S. aureus DNA gyrase, and causes downregulation of mulitple essential proteins. With light irradiation, TPA-1 showed excellent antiplanktonic and antibiofilm activities against S. aureus and P. aeruginosa by generating reactive oxygen species that cause membrane damage. Furthermore, TPA-1 under light irradiation can significantly reduce the number of viable bacteria in biofilms and promote wound healing in methicillin-resistant S. aureus (MRSA) and P. aeruginosa-infected mice models
Project description:Optimisation of DNA-protein co-extraction from the thin microbial biofilm inhabiting marine plastic debris for meta-omics and comparative metaproteomics analysis.
Project description:ovariectomized mice treated with E2+Progesterone, E2+Progesterone+TPA, E2+Progesterone+RU486 and sham for 14 days, followed by isolation of luminal mature, luminal progenitor and mammary stem cells through FACS and RNASeq performed for each cell lineage population. TPA and RU486 treated mice show significant decline in mammary stem cell pool pulation comapared to EP treated mice
Project description:Salmonella spp. biofilms have been implicated in persistence in the environment and plant surfaces. In addition, Salmonella is able to form biofilms on the surface on cholesterol gallstones. The ability of Salmonella spp. on these surfaces is superior to biofilm formation on surfaces on glass or plastic. Thus, we hypothesized that Salmonella gene expression is specific during biofilm development on cholesterol surfaces.
Project description:The basic two-step terminal differentiation model of the medullary thymic epithelial cell (mTEC) lineage from immature MHCIIlo to mature MHCIIhi mTECs has recently been extended to include a third stage namely the post-Aire MHCIIlo subset as identified by lineage-tracing models. Yet, a suitable surface marker distinguishing the phenotypically overlapping pre- from the post-Aire immature MHCIIlo stage has been lacking. Here, we introduce the lectin Tetragonolobus purpureas agglutinin (TPA) as a novel cell surface marker that allows for such delineation. Based on our data, we derived the following sequence of mTEC differentiation: TPA- MHCIIlo → TPA- MHCIIhi → TPA+ MHCIIhi → TPA+ MHCIIlo. Surprisingly, in the steady-state postnatal thymus most immature TPA- pre-Aire rather than terminally differentiated post-Aire TPA+ MHCIIlo mTECs were marked for apoptosis at an exceptionally high rate of about 70 %. Hence, only the minor cycling fraction of the MHCIIlo subset (< 20 %) potentially qualified as mTEC precursors. FoxN1 expression inversely correlated with the fraction of slow cycling and apoptotic cells within the four TPA subsets. TPA further sub-divided human mTECs, though with different subset distribution. Our revised roadmap emphazises close parallels of terminal mTEC development with that of skin, undergoing an alternative route of cell death namely cornification rather than apoptosis. The high rate of apoptosis in immature pre-Aire mTECs points to a “quality control” step during early mTEC differentiation.
Project description:The authors of this manuscript suggest the stoichiometry of outer submodules of the budding yeast kinetochore is strongly influenced by factors at the kinetochore-microtubule interface, including Fin1, Dam1, and microtubule tracking. Outer kinetochore stoichiometry is remarkably plastic and responsive to microtubule-proximal regulation.