Hasil untuk "Microbiology"

J. Prosser, B. Bohannan, T. Curtis et al.

D. McDougald, S. Rice, N. Barraud et al.

F. Asnicar, A. M. Thomas, Andrea Passerini et al.

Shu-Jun Ma, Ke-Fang Xie, Jie-Lin Duan et al.

ABSTRACT Non-receptor tyrosine kinase c-Abl is critical for host defense against bacterial and viral infections, yet its role in antifungal immunity remains elusive. Here, we report that inhibition of c-Abl with flumatinib mesylate significantly impairs the survival rate and exacerbates fungal burden in mice infected with Candida albicans. Our findings reveal that c-Abl inhibition reduces production of TNF-α, IL-10, and IL-12 in bone marrow-derived dendritic cells (BMDCs) after stimulation with fungal β-glucan or α-mannan. Mechanistically, c-Abl inhibition significantly blocks p38 and extracellular signal-regulated kinases 1/2 (ERK1/2) activation in BMDCs after α-mannan stimulation in a c-Cbl dependent manner. Collectively, our study uncovers a c-Abl/c-Cbl/MAPK signaling axis in dendritic cells that governs antifungal innate immunity, highlighting c-Cbl as a critical downstream mediator linking c-Abl to host defense against C. albicans. Our findings provide a mechanistic basis for fungal risk assessment in cancer patients treated with c-Abl inhibitors.

Pu Chen, Junli Chen, Nan Xu et al.

Abstract Background Recent advances in understanding gut‒liver axis homeostasis has been made because of the promising beneficial effects of these systems on health maintenance and performance promotion. However, little is known about the effects of long-term microgravity exposure on the gut-liver axis or about effective countermeasures to prevent disruptions in gut-liver axis homeostasis. Hence, we conducted a well-controlled study to determine the effects of long-term microgravity exposure on liver activity, the gut microbiota and gut-liver axis homeostasis via a hindlimb suspension rat model. Method The animal model suffering microgravity exposure was achieved using hindlimb unloading approaches. Afterwards, the histomorphology of liver and colon was acquired using hematoxylin-eosin (H&E) staining and the lipid accumulation was observed by oil red O staining. Plasm/serum indexes were detected by Enzyme-linked immunosorbent assay (ELISA) analysis. In addition, the gut microbiota was characterized through 16S rRNA gene Sequencing and the metabolome was conducted on UHPLC‒MS/MS system. Results Interestingly, long-term microgravity exposure increased lipid deposition, oxidative stress and inflammation in the liver; increased proportions of opportunistic enteric pathogens; and disrupted intestinal barrier integrity, paralleling with dysregulation of gut-liver axis homeostasis, which especially underlined portal influx of secondary bile acid (mainly ursodeoxycholic acid and lithocholic acid) and tryptophan metabolism. Conclusion Taken together, our findings suggest that gut microbiota is an effective target for maintaining gut-liver axis homeostasis as well as protecting astronauts from inflammation when deal with microgravity exposure in further long-term manned space mission.

Daniela V. Staton, Jonah Tang, Matthew Barbisan et al.

Background Although touted as a safer alternative to cigarette smoking, electronic cigarette usage has been increasingly linked to a myriad of health issues and appears to impact the oral microbiome. Meanwhile, nitrate supplementation has shown promise as a prebiotic that induces positive effects on the oral microbiome.Methods In this pilot study, the impact of nitrate supplementation as a countermeasure to e-cigarette usage was explored using in vitro growth and 16S rRNA analysis of microcosms derived from e-cigarette users and nonusers and supplementation with nitrate-rich beetroot juice extract.Results The impacts of e-cigarette usage and beetroot supplementation were somewhat limited, with beetroot juice extract supplementation having a significant impact on diversity according to some, but not all, diversity metrics examined. The saliva of the e-cigarette users was depleted in nitrate-reducing Neisseria spp. In terms of differentially abundant individual taxa, the addition of beetroot juice extract to the saliva-derived microcosms had a larger impact on the communities derived from the e-cigarette users compared to that of the nonusers.Conclusions Overall, this limited pilot study suggests that beetroot juice extract supplementation may impact the microbiota of e-cigarette users and adds to contemporary research paving the way for more in-depth studies examining the role of nitrate-rich supplements as prebiotics to promote oral health.

Segawa Yuhiro, Nakamura Akiho, Hashiguchi Hiroki et al.

Si Young Lee, Hye Young Yoon

Background: To understand the process of biofilm formation in dental unit waterlines (DUWLs), it is necessary to assess the of bacteria that constitute DUWL biofilms. This study assessed the coaggregation of bacterial species isolated from DUWL biofilms and other related mechanisms. Methods: Coaggregation was macroscopically evaluated. Cultures of the DUWLs isolates were adjusted to the same concentration (optical density [OD]600=1.5). The isolates were mixed in pairs and incubated for 1 hour at room temperature. Subsequently, the coaggregation values were scored. Some coaggregation pairs were observed through fluorescence microscope after staining with SYTOⓇ 9 and propidium iodide. To assess their coaggregation properties, inhibition of coaggregation was performed by adding sugars and amino acids to the coaggregation pairs and the coaggregation values were scored again post-addition. Results: Coaggregation was observed in 360 out of 406 coaggregation pairs, whose coaggregation scores of ranged from one to three points. Five pairs (1.4%) had a coaggregation score of 3 points. Among these five pairs, mannose most frequently inhibited coaggregation. Among the isolates, Cupriavidus pauculus HY12 and Beijerinckia derxii subsp. venezuelae HY7 had the highest number of coaggregation pairs, with scores of 2 and 3. Conclusion: Cupriavidus pauculus HY12 and B. derxii subsp. venezuelae HY7 form many coaggregation pairs and may play important roles in biofilm maturation. The results of this study can be used to propose methods to inhibit the formation of DUWL biofilms by inhibiting coaggregation.

Letizia Crocetti, Andrei I. Khlebnikov, Gabriella Guerrini et al.

Chronic inflammation contributes to a number of diseases. Therefore, control of the inflammatory response is an important therapeutic goal. To identify novel anti-inflammatory compounds, we synthesized and screened a library of 80 pyrazolo[1,5-<i>a</i>]quinazoline compounds and related derivatives. Screening of these compounds for their ability to inhibit lipopolysaccharide (LPS)-induced nuclear factor κB (NF-κB) transcriptional activity in human THP-1Blue monocytic cells identified 13 compounds with anti-inflammatory activity (IC₅₀ < 50 µM) in a cell-based test system, with two of the most potent being compounds <b>13i</b> (5-[(4-sulfamoylbenzyl)oxy]pyrazolo[1,5-<i>a</i>]quinazoline-3-carboxamide) and <b>16</b> (5-[(4-(methylsulfinyl)benzyloxy]pyrazolo[1,5-<i>a</i>]quinazoline-3-carboxamide). Pharmacophore mapping of potential targets predicted that <b>13i</b> and <b>16</b> may be ligands for three mitogen-activated protein kinases (MAPKs), including extracellular signal-regulated kinase 2 (ERK2), p38α, and <i>c</i>-Jun <i>N</i>-terminal kinase 3 (JNK3). Indeed, molecular modeling supported that these compounds could effectively bind to ERK2, p38α, and JNK3, with the highest complementarity to JNK3. The key residues of JNK3 important for this binding were identified. Moreover, compounds <b>13i</b> and <b>16</b> exhibited micromolar binding affinities for JNK1, JNK2, and JNK3. Thus, our results demonstrate the potential for developing lead anti-inflammatory drugs based on the pyrazolo[1,5-<i>a</i>]quinazoline and related scaffolds that are targeted toward MAPKs.

Xavier Sánchez-Sáez, Isabel Ortuño-Lizarán, Carla Sánchez-Castillo et al.

Abstract Background The main clinical symptoms characteristic of Parkinson’s disease (PD) are bradykinesia, tremor, and other motor deficits. However, non-motor symptoms, such as visual disturbances, can be identified at early stages of the disease. One of these symptoms is the impairment of visual motion perception. Hence, we sought to determine if the starburst amacrine cells, which are the main cellular type involved in motion direction selectivity, are degenerated in PD and if the dopaminergic system is related to this degeneration. Methods Human eyes from control (n = 10) and PD (n = 9) donors were available for this study. Using immunohistochemistry and confocal microscopy, we quantified starburst amacrine cell density (choline acetyltransferase [ChAT]-positive cells) and the relationship between these cells and dopaminergic amacrine cells (tyrosine hydroxylase-positive cells and vesicular monoamine transporter-2-positive presynapses) in cross-sections and wholemount retinas. Results First, we found two different ChAT amacrine populations in the human retina that presented different ChAT immunoreactivity intensity and different expression of calcium-binding proteins. Both populations are affected in PD and their density is reduced compared to controls. Also, we report, for the first time, synaptic contacts between dopaminergic amacrine cells and ChAT-positive cells in the human retina. We found that, in PD retinas, there is a reduction of the dopaminergic synaptic contacts into ChAT cells. Conclusions Taken together, this work indicates degeneration of starburst amacrine cells in PD related to dopaminergic degeneration and that dopaminergic amacrine cells could modulate the function of starburst amacrine cells. Since motion perception circuitries are affected in PD, their assessment using visual tests could provide new insights into the diagnosis of PD.

Emily A. Henderson, Slawomir Lukomski, Slawomir Lukomski et al.

Pancreatic cancer is a highly aggressive form of cancer with a five-year survival rate of only ten percent. Pancreatic ductal adenocarcinoma (PDAC) accounts for ninety percent of those cases. PDAC is associated with a dense stroma that confers resistance to current treatment modalities. Increasing resistance to cancer treatments poses a challenge and a need for alternative therapies. Bacterial mediated cancer therapies were proposed in the late 1800s by Dr. William Coley when he injected osteosarcoma patients with live streptococci or a fabrication of heat-killed Streptococcus pyogenes and Serratia marcescens known as Coley’s toxin. Since then, several bacteria have gained recognition for possible roles in potentiating treatment response, enhancing anti-tumor immunity, and alleviating adverse effects to standard treatment options. This review highlights key bacterial mechanisms and structures that promote anti-tumor immunity, challenges and risks associated with bacterial mediated cancer therapies, and applications and opportunities for use in PDAC management.

I. A. Kirillov, A. P. Pirozhkov, V. V. Rubtsov et al.

In November 2020, the Armed Forces of the Russian Federation began mass immunisation of the personnel with Gam-COVID-Vac (Sputnik V), the first Russia vaccine against the new coronavirus infection (COVID-19). Thus, it became necessary to assess post-vaccination antibody levels and the duration and intensity of humoral immunity to COVID-19.The aim of the study was to investigate the immunogenicity and efficacy of Gam-COVID-Vac in military medical staff after vaccination.Materials and methods: the authors determined the presence of specific antibodies in the serum of individuals immunised with Gam-COVID-Vac (477 volunteers) and COVID-19 convalescents (73 patients), using virus neutralisation (VN), enzyme-linked immunosorbent assay (ELISA) with reagent kits by several manufacturers, and immunoblotting. The results of the study were evaluated using analysis of variance.Results: VN detected virus neutralising antibodies in 90.7% of vaccinated subjects; ELISA, in 95.4%. Both VN and ELISA showed lower antibody levels in the vaccinated over 50 years of age. ELISA demonstrated a significantly higher concentration of anti-SARS-CoV-2 spike IgG in the Gam-COVID-Vac group than in the COVID-19 convalescent group. The correlation between antibody detection results by VN and ELISA was the strongest when the authors used their experimental reagent kit for quantitative detection of virus neutralising antibodies by competitive ELISA with the recombinant human ACE2 receptor. Having analysed the time course of neutralising antibody titres, the authors noted a significant, more than two-fold decrease in geometric means of the titres three months after administration of the second vaccine component.Conclusions: the subjects vaccinated with Gam-COVID-Vac gain effective humoral immunity to COVID-19. The decrease in titres indicates the need for revaccination in 6 months.

Mateus Neri Oliveira Reis, Luciana Cristina Vitorino, Lucas Loram Lourenço et al.

Considering a scenario where there is a low availability and increasing costs of fertilizers in the global agricultural market, as well as a finitude of important natural resources, such as phosphorus (P), this study tested the effect of the inoculation of rhizospheric or endophytic microorganisms isolated from <i>Hymenaea courbaril</i> and <i>Butia purpurascens</i> on the growth promotion of <i>Glycine max</i> (L.) Merr. The tests were conducted in a controlled greenhouse system, and the effects of biofertilization were evaluated using the following parameters: dry biomass, nutritional content, and photochemical and photosynthetic performance of plants. Seed biopriming was performed with four bacterial and four fungal isolates, and the results were compared to those of seeds treated with the commercial product Biomaphos^®. Overall, microbial inoculation had a positive effect on biomass accumulation in <i>G. max</i>, especially in strains PA12 (<i>Paenibacillus alvei</i>), SC5 (<i>Bacillus cereus</i>), and SC15 (<i>Penicillium sheari</i>). The non-inoculated control plants accumulated less nutrients, both in the whole plant and aerial part, and had reduced chlorophyll index and low photosynthetic rate (<i>A</i>) and photochemical efficiency. Strains PA12 (<i>P. alvei</i>), SC5 (<i>B. cereus</i>), and 328EF (<i>Codinaeopsis</i> sp.) stood out in the optimization of nutrient concentration, transpiration rate, and stomatal conductance. Plants inoculated with the bacterial strains PA12 (<i>P. alvei</i>) and SC5 (<i>B. cereus</i>) and with the fungal strains 328EF (<i>Codinaeopsis</i> sp.) and SC15 (<i>P. sheari</i>) showed the closest pattern to that observed in plants treated with Biomaphos^®, with the same trend of direction of the means associated with chlorophyll index, (<i>A</i>), dry mass, and concentration of important nutrients such as N, P, and Mg. We recommend the use of these isolates in field tests to validate these strains for the production of biological inoculants as part of the portfolio of bioinputs available for <i>G. max</i>.

Shohei Yasuda, Toshikazu Suenaga, Laura Orschler et al.

Upcycling wastes into valuable products by mixed microbial communities has recently received considerable attention. Sustainable production of high-value substances from one-carbon (C1) compounds, e.g., methanol supplemented as an external electron donor in bioreactors for wastewater treatment, is a promising application of upcycling. This study undertook a gene-centric approach to screen valuable production potentials from mixed culture biomass, removing organic carbon and nitrogen from landfill leachate. To this end, the microbial community of the activated sludge from a landfill leachate treatment plant and its metabolic potential for the production of seven valuable products were investigated. The DNA extracted from the activated sludge was subjected to shotgun metagenome sequencing to analyze the microbial taxonomy and functions associated with producing the seven products. The functional analysis confirmed that the activated sludge could produce six of the valuable products, ectoine, polyhydroxybutyrate (PHB), zeaxanthin, astaxanthin, acetoin, and 2,3-butanediol. Quantification of the detected functional gene hit numbers for these valuable products as a primary trial identified a potential rate-limiting metabolic pathway, e.g., conversion of L-2,4-diaminobutyrate into N-γ-acetyl-L2,4,-diaminobutyrate during the ectoine biosynthesis. Overall, this study demonstrated that primary screening by the proposed gene-centric approach can be used to evaluate the potential for the production of valuable products using mixed culture or single microbe in engineered systems. The proposed approach can be expanded to sites where water purification is highly required, but resource recovery, or upcycling has not been implemented.

Devadathan Valiyamangalath Sethumadhavan, CA Jabeena, Gayathri Govindaraju et al.

The emergence of COVID-19, caused by SARS-CoV-2 poses a significant threat to humans as it is highly contagious with increasing mortality. There exists a high degree of heterogeneity in the mortality rates of COVID-19 across the globe. There are multiple speculations on the varying degree of mortality. Still, all the clinical reports have indicated that preexisting chronic diseases like hypertension, diabetes, chronic obstructive pulmonary disease (COPD), kidney disorders, and cardiovascular diseases are associated with the increased risk for high mortality in SARS-CoV-2 infected patients. It is worth noting that host factors, mainly epigenetic factors could play a significant role in deciding the outcome of COVID-19 diseases. Over the recent years, it is evident that chronic diseases are developed due to altered epigenome that includes a selective loss/gain of DNA and histone methylation on the chromatin of the cells. Since, there is a high positive correlation between chronic diseases and elevated mortality due to SARS-CoV-2, in this review; we discuss the overall picture of the aberrant epigenome map in varying chronic ailments and its implications in COVID-19 disease severity and high mortality.

Agafonov Alexander V., Emtseva Maria V., Shabanova (Kobozeva) Elena V.

According to descriptions, the Siberian species E. peschkovae and E. confusus differ in the presence or absence of trichomes on lemma and rachilla surfaces only. Two methods were used for study microevolutionary relationships between these species: hybridization of biotypes from different locations and analysis of nucleotide sequences of the low-copy nuclear gene GBSS1. Created and grown hybrids in combinations AMU-8804 × BER-0807 and AMU-8804 × BUK-1109 showed complete seed sterility in two field vegetations. Taking into account wide species areas, 3 hybrids were created between Magadan biotypes from a common habitat in the combination E. confusus MOL1887 × E. peschkovae MOL-1882. The plants showed seed fertility (SF) of 0–3 %. This result does not obscure the possibility to assess SF in the F2 generation and the character of inheritance of diagnostic traits. A comparative study of the GBSS1 gene sequences in accessions was carried out in comparison with clones of reference species. Differentiation of clones by the St2 subgenome in E. confusus, E. peschkovae, E. sibiricus and E. caninus did not reveal a clear relationships between the species. Meanwhile, a certain species specificity for the H1 subgenome was noted, confirming the existence of microevolutionary isolation of these species.

Yue Ao, Chongrui Yang, Shengchen Wang et al.

Summary The potential utility of black soldier fly larvae (BSFL) to convert animal waste into harvested protein or lipid sources for feeding animal or producing biodiesel provides a new strategy for agricultural waste management. In this study, the taxonomic structure and potential metabolic and nutrient functions of the intestinal bacterial communities of BSFL were investigated in chicken and swine manure conversion systems. Proteobacteria, Firmicutes and Bacteroidetes were the dominant phyla in the BSFL gut in both the swine and chicken manure systems. After the larvae were fed manure, the proportion of Proteobacteria in their gut significantly decreased, while that of Bacteroidetes remarkably increased. Compared with the original intestinal bacterial community, approximately 90 and 109 new genera were observed in the BSFL gut during chicken and swine manure conversion, and at least half of the initial intestinal genera found remained in the gut during manure conversion. This result may be due to the presence of specialized crypts or paunches that promote microbial persistence and bacteria–host interactions. Ten core genera were found in all 21 samples, and the top three phyla among all of the communities in terms of relative abundance were Proteobacteria, Firmicutes and Bacteroidetes. The nutrient elements (OM, TN, TP, TK and CF) of manure may partly affect the succession of gut bacterial communities with one another, while TN and CF are strongly positively correlated with the relative abundance of Providencia. Some bacterial taxa with the reported ability to synthesize amino acids, Rhizobiales, Burkholderia, Bacteroidales, etc., were also observed in the BSFL gut. Functional analysis based on genes showed that intestinal microbes potentially contribute to the nutrition of BSFL and the high‐level amino acid metabolism may partly explain the biological mechanisms of protein accumulation in the BSFL body. These results are helpful in understanding the biological mechanisms of high‐efficiency nutrient conversion in BSFL associated with intestinal microbes.

Lilly Cheng Immergluck, Traci Leong, Khusdeep Malhotra et al.

Abstract Background Community- associated methicillin resistant Staphylococcus aureus (CA-MRSA) cause serious infections and rates continue to rise worldwide. Use of geocoded electronic health record (EHR) data to prevent spread of disease is limited in health service research. We demonstrate how geocoded EHR and spatial analyses can be used to identify risks for CA-MRSA in children, which are tied to place-based determinants and would not be uncovered using traditional EHR data analyses. Methods An epidemiology study was conducted on children from January 1, 2002 through December 31, 2010 who were treated for Staphylococcus aureus infections. A generalized estimated equations (GEE) model was developed and crude and adjusted odds ratios were based on S. aureus risks. We measured the risk of S. aureus as standardized incidence ratios (SIR) calculated within aggregated US 2010 Census tracts called spatially adaptive filters, and then created maps that differentiate the geographic patterns of antibiotic resistant and non-resistant forms of S. aureus. Results CA-MRSA rates increased at higher rates compared to non-resistant forms, p = 0.01. Children with no or public health insurance had higher odds of CA-MRSA infection. Black children were almost 1.5 times as likely as white children to have CA-MRSA infections (aOR 95% CI 1.44,1.75, p < 0.0001); this finding persisted at the block group level (p < 0.001) along with household crowding (p < 0.001). The youngest category of age (< 4 years) also had increased risk for CA-MRSA (aOR 1.65, 95%CI 1.48, 1.83, p < 0.0001). CA-MRSA encompasses larger areas with higher SIRs compared to non-resistant forms and were found in block groups with higher proportion of blacks (r = 0.517, p < 0.001), younger age (r = 0.137, p < 0.001), and crowding (r = 0.320, p < 0.001). Conclusions In the Atlanta MSA, the risk for CA-MRSA is associated with neighborhood-level measures of racial composition, household crowding, and age of children. Neighborhoods which have higher proportion of blacks, household crowding, and children < 4 years of age are at greatest risk. Understanding spatial relationship at a community level and how it relates to risks for antibiotic resistant infections is important to combat the growing numbers and spread of such infections like CA-MRSA.

Salih Hosoglu, Eyup Arslan, Emel Aslan et al.

Introduction: Multi-drug resistant Acinetobacter baumannii (MDR-Ab) infections are an important healthcare problem globally. The aim of this study was to evaluate risk factors associated with MDR-Ab infections in hospitalized patients in Turkey. Methodology: A case-control study was performed in a tertiary care 1,303-bed university hospital, among case patients with MDR-Ab infections. The hospital records of case and control patients were retrospectively evaluated over a year. Patients who were hospitalized in the same department and in the same time interval as the case patients, without MDR-Ab infection or colonization, were chosen for control group. Demographic characteristics, Acute Physiology And Chronic Health Evaluation II (APACHE II) scores, comorbid diseases, use of invasive tools and duration of usage, and duration of use of antibiotics were recorded for all patients. Comparisons between case and control groups for possible risk factors were performed. Results: In total, 95 cases and 95 controls were included in the study. Univariate analysis highlighted several variables as risk factors for MDR-Ab infections. Multivariate analysis showed that only antibiotic usage over seven days (OR = 2.38, CI = 1.18-4.83, p = 0.016) was found to be a significant risk factor. When antibiotic treatment patterns in both groups were compared, the use of carbapenems (p = 0.001) and glycopeptide antibiotics (p=0.001) in patient treatment were found significantly higher in the MDR-Ab case group. Conclusion: This study showed us that previous antibiotic use is a significant risk factor for MDR-Ab infections. The use of carbapenems and glycopeptides should be considered as primary risk factors for developing MDR-Ab infection.

L. Huang, W. Lai, L. Zhu et al.