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Overdue Therapy associated with Climbing down from Aortic Coarctation Brings about Anterior Cerebral Split: An instance Report.
ntial additional bias depending on the quantification method being used.Fusobacterium nucleatum is a common oral bacterium that is enriched in colorectal adenomas and adenocarcinomas (CRC). In humans, high fusobacterial CRC abundance is associated with chemoresistance and poor prognosis. In animal models, fusobacteria accelerate CRC progression. Targeting F. nucleatum may reduce fusobacteria cancer progression and therefore determining the origin of CRC F. nucleatum and the route by which it reaches colon tumors is of biologic and therapeutic importance. Arbitrarily primed PCR performed previously on matched same-patients CRC and saliva F. nucleatum isolates, suggested that CRC F. nucleatum may originate from the oral cavity. However, the origin of CRC fusobacteria as well as the route of their arrival to the tumor have not been well-established. Herein, we performed and analyzed whole genome sequencing of paired, same-patient oral, and CRC F. nucleatum isolates and confirmed that CRC-fusobacteria originate from the oral microbial reservoir. Oral fusobacteria may translocate to CRC by descending via the digestive tract or using the hematogenous route during frequent transient bacteremia caused by chewing, daily hygiene activities, or dental procedures. Using the orthotropic CT26 mouse model we previously showed that IV injected F. nucleatum colonize CRC. #link# Here, we compared CRC colonization by gavage vs. intravenous inoculated F. nucleatum in the MC38 and CT26 mouse orthotropic CRC models. Under the tested conditions, hematogenous fusobacteria were more successful in CRC colonization than gavaged ones. Our results therefore provide evidence that the hematogenous route may be the preferred way by which oral fusobacteria reach colon tumors.Human microbiome studies remain focused on bacteria, as they comprise the dominant component of the microbiota. Recent advances in sequencing technology and optimization of amplicon sequencing protocols have allowed the description of other members of the microbiome, including eukaryotes (fungi) and, most recently, archaea. There are no known human-associated archaeal pathogens. Their diversity and contribution to health and chronic respiratory diseases, such as chronic rhinosinusitis (CRS), are unknown. Patients with CRS suffer from long-term sinus infections, and while the microbiota is hypothesized to play a role in its pathogenesis, the exact mechanism is poorly understood. In this cross-sectional study, we applied a recently optimized protocol to describe the prevalence, diversity and abundance of archaea in swab samples from the middle meatus of 60 individuals with and without CRS. A nested PCR approach was used to amplify the archaeal 16S rRNA gene for sequencing, and bacterial and archaeal load (also based on 16S rRNA genes) were estimated using Droplet Digital™ PCR (ddPCR). A total of 16 archaeal amplicon sequence variants (ASVs) from the phyla Euryarchaeota and Thaumarchaeota were identified. Archaeal ASVs were detected in 7/60 individuals, independent of disease state, whereas bacterial ASVs were detected in 60/60. Bacteria were also significantly more abundant than archaea. The ddPCR method was more sensitive than amplicon sequencing at detecting archaeal DNA in samples. Phylogenetic trees were constructed to visualize the evolutionary relationships between archaeal ASVs, isolates and clones. ASVs were placed into phylogenetic clades containing an apparent paucity of human-associated reference sequences, revealing how little studied the human archaeome is. This is the largest study to date to examine the human respiratory-associated archaeome, and provides the first insights into the prevalence, diversity and abundance of archaea in the human sinuses.Candida auris has emerged as a medically important pathogen with considerable resistance to antifungal agents. The ability to produce biofilms is an important pathogenicity feature of this species that aids escape of host immune responses and antimicrobial agents. The objective of this study was to verify antifungal action using in vitro and in vivo models of the Lactobacillus paracasei 28.4 probiotic cells and postbiotic activity of crude extract (LPCE) and fraction 1 (LPF1), derived from L. paracasei 28.4 supernatant. Both live cells and cells free supernatant of L. link2 paracasei 28.4 inhibited C. auris suggesting probiotic and postbiotic effects. The minimum inhibitory concentration (MIC) for LPCE was 15 mg/mL and ranges from 3.75 to 7.5 mg/mL for LPF1. Killing kinetics determined that after 24 h treatment with LPCE or LPF1 there was a complete reduction of viable C. auris cells compared to fluconazole, which decreased the initial inoculum by 1-logCFU during the same time period. LPCE and LPF1 significantly reduced the biomass (p = 0.0001) and the metabolic activity (p = 0.0001) of C. auris biofilm. There was also a total reduction (~108 CFU/mL) in viability of persister C. auris cells after treatment with postbiotic elements (p less then 0.0001). In an in vivo study, injection of LPCE and LPF1 into G. mellonella larvae infected with C. auris prolonged survival of these insects compared to a control group (p less then 0.05) and elicited immune responses by increasing the number of circulating hemocytes and gene expression of antimicrobial peptide galiomicin. We concluded that the L. paracasei 28.4 cells and postbiotic elements (LPCE and LPF1) have antifungal activity against planktonic cells, biofilms, and persister cells of C. auris. Postbiotic supplementation derived from L. paracasei 28.4 protected G. mellonella infected with C. auris and enhanced its immune status indicating a dual function in modulating a host immune response.Chronic infections present a serious economic burden to health-care systems. The severity and prevalence of chronic infections are continuously increasing due to an aging population and an elevated number of lifestyle related diseases such as diabetes. Treatment of chronic infections has proven difficult, mainly due to the presence of biofilms that render bacteria more tolerant toward antimicrobials and the host immune response. Chronic infections have been described to harbor several different bacterial species and it has been hypothesized that microscale interactions and mixed-species consortia are present as described for most natural occurring biofilms i.e., aquatic systems and industrial settings, but also for some commensal human biofilms i.e., the mouth microbiota. However, the presence of mixed-species biofilms in chronic infections is most often an assumption based on culture-based methods and/or by means of molecular approaches, such as PCR and sequencing performed from homogenized bulk tissue samples. These methods disregard the spatial organization of the bacterial community and thus valuable information on biofilm aggregate composition, spatial organization, and possible interactions between different species is lost. Hitherto, only find more have made visual in situ presentations of mixed-species biofilms in chronic infections, which is pivotal for the description of bacterial composition, spatial distribution, and interspecies interaction on the microscale. In order for bacteria to interact (synergism, commensalism, mutualism, competition, etc.) they need to be in close proximity to each other on the scale where they can affect e.g., solute concentrations. We argue that visual proof of mixed species biofilms in chronic infections is scarce compared to what is seen in e.g., environmental biofilms and call for a debate on the importance of mixed-species biofilm in chronic infections.Despite efficient virological suppression on antiretroviral therapy (ART), people living with HIV (PLWH), experience an increased burden of premature co-morbidities, such as cancer and end-organ disease. link3 With remaining challenges in terms of access to therapy, adherence and potential long-term drug toxicity, improving their long-term healthcare outcome, including new strategies for HIV clearance, remains a global priority. There is, therefore, an ongoing need to better characterize and harness the immune response in order to develop new strategies and supplement current therapeutic approaches for a "functional" cure. Current efforts toward HIV eradication to enhance immune recognition and elimination of persistently infected cells have highlighted the need for an optimized "kill" approach. Natural killer (NK) cells play an important role in antiviral defense and by virtue of their innate and adaptive features hold great promise as a focus of "kill" efforts. Galvanized by advances in the cancer field, NK cell exploitation, represents a transformative approach to augment HIV therapeutic modalities, circumventing many of the limitations inherent to T cell approaches. In this review we will discuss recent advances in our understanding of the development of NK cell adaptive/memory responses in HIV infection and highlight new and exciting opportunities to exploit the beneficial attributes of NK cells for HIV immunotherapy.Paracoccidioides brasiliensis is a temperature-dependent dimorphic fungus that causes systemic paracoccidioidomycosis, a granulomatous disease. The massive production of reactive oxygen species (ROS) by the host's cellular immune response is an essential strategy to restrain the fungal growth. Among the ROS, the hydroperoxides are very toxic antimicrobial compounds and fungal peroxidases are part of the pathogen neutralizing antioxidant arsenal against the host's defense. Among them, the peroxiredoxins are highlighted, since some estimates suggest that they are capable of decomposing most of the hydroperoxides generated in the host's mitochondria and cytosol. We presently characterized a unique P. brasiliensis 1-Cys peroxiredoxin (PbPrx1). Our results reveal that it can decompose hydrogen peroxide and organic hydroperoxides very efficiently. We showed that dithiolic, but not monothiolic compounds or heterologous thioredoxin reductant systems, were able to retain the enzyme activity. Structural analysis revealed that PbPrx1 has an α/β structure that is similar to the 1-Cys secondary structures described to date and that the quaternary conformation is represented by a dimer, independently of the redox state. We investigated the PbPrx1 localization using confocal microscopy, fluorescence-activated cell sorter, and immunoblot, and the results suggested that it localizes both in the cytoplasm and at the cell wall of the yeast and mycelial forms of P. brasiliensis, as well as in the yeast mitochondria. Our present results point to a possible role of this unique P. brasiliensis 1-Cys Prx1 in the fungal antioxidant defense mechanisms.Malassezia includes yeasts belong to the subphylum Ustilaginomycotina within the Basidiomycota. Malassezia yeasts are commonly found as commensals on human and animal skin. Nevertheless, Malassezia species are also associated with several skin disorders, such as dandruff/seborrheic dermatitis, atopic eczema, pityriasis versicolor, and folliculitis. More recently, associations of Malassezia with Crohn's disease, pancreatic ductal adenocarcinoma, and cystic fibrosis pulmonary exacerbation have been reported. The increasing availability of genomic and molecular tools have played a crucial role in understanding the genetic basis of Malassezia commensalism and pathogenicity. In the present review we report genomics advances in Malassezia highlighting unique features that potentially impacted Malassezia biology and host adaptation. Furthermore, we describe the recently developed protocols for Agrobacterium tumefaciens-mediated transformation in Malassezia, and their applications for random insertional mutagenesis or targeted gene replacement strategies.
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