Biology subjects

An, D.

Publications and source records attributed to An, D..

25 records · Page 2Linked to original sources

bioRxiv2019

Biocontrol of PGPR strain Bacillus amyloliquefaciens Ba168 against Phytophthora nicotianae on tobacco

Tobacco black shank (TBS) caused by Phytophthora nicotianae is destructive to almost all kinds of tobacco cultivars and is widespread in many tobacco-planted countries. Here, an isolated plant growth-promoting rhizobacteria (PGPR) strain Ba168 is promise in biocontrol of TBS. In vitro assays disclosed a strong P. nicotianae suppression activity and the field utilization potential (FUP) by characterized the crude extract of culture filtrates of Ba168. P. nicotianaes growth was inhibited by the crude extract at minimum inhibitory concentration (MIC) of 5l/mL. Extracellular conductivity, pH and the wet, dry weight of P. nicotianaes mycelia, were significantly different after treated with different concentrations of the crude extract and the deformity and perforation of treated P. nicotianaes hyphae can be observed in scanning electron microscope (SEM) analysis. Proteome characterizations of the crude extract were used as supplementary proofs that further evaluated FUP of Ba168. We then identified strain Ba168 as B. amyloliquefaciens by its genetic and phenotypic characteristics. Field assays comparatively evaluated TBS control efficacy of these PGPRs and agrochemicals. Pooling analysis of the results showed that the biocontrol efficacy of Ba168 preparation is only lower than Mixture of Propamocarb hydrochloride and Azoxystrobin (MPA) but better than other tested subjects. Although the existence of differences in biocontrol efficacy, PGPR preparations effectively reduced the disease index of tobacco.\n\nImportanceThis work demonstrates the promising biocontrol potential of B. amyloliquefaciens Ba168 and highlights the positive roles of PGPR in suppression of this soil-borne disease.

microbiology↗

bioRxiv2019

Stem cell-derived cranial and spinal motor neurons reveal proteostatic differences between ALS resistant and sensitive motor neurons

In amyotrophic lateral sclerosis (ALS) spinal motor neurons (SpMN) progressively degenerate while a subset of cranial motor neurons (CrMN) are spared until late stages of the disease. Using a rapid and efficient protocol to differentiate mouse embryonic stem cells (ESC) to SpMNs and CrMNs, we now report that ESC-derived CrMNs accumulate less human (h)SOD1 and insoluble p62 than SpMNs over time. ESC-derived CrMNs have higher proteasome activity to degrade misfolded proteins and are intrinsically more resistant to chemically-induced proteostatic stress than SpMNs. Chemical and genetic activation of the proteasome rescues SpMN sensitivity to proteostatic stress. In agreement, the hSOD1 G93A mouse model reveals that ALS-resistant CrMNs accumulate less insoluble hSOD1 and p62-containing inclusions than SpMNs. Primary-derived ALS-resistant CrMNs are also more resistant than SpMNs to proteostatic stress. Thus, an ESC-based platform has identified a superior capacity to maintain a healthy proteome as a possible mechanism to resist ALS-induced neurodegeneration.

neuroscience↗

bioRxiv2019

A global perspective on microbial diversity in the terrestrial deep subsurface

While recent efforts to catalogue Earths microbial diversity have focused upon surface and marine habitats, 12% to 20% of Earths bacterial and archaeal biomass is suggested to inhabit the terrestrial deep subsurface, compared to [~]1.8% in the deep subseafloor 1-3. Metagenomic studies of the terrestrial deep subsurface have yielded a trove of divergent and functionally important microbiomes from a range of localities 4-6. However, a wider perspective of microbial diversity and its relationship to environmental conditions within the terrestrial deep subsurface is still required. Here, we show the diversity of bacterial communities in deep subsurface groundwater is controlled by aquifer lithology globally, by using 16S rRNA gene datasets collected across five countries on two continents and from fifteen rock types over the past decade. Furthermore, our meta-analysis reveals that terrestrial deep subsurface microbiota are dominated by Betaproteobacteria, Gammaproteobacteria and Firmicutes, likely as a function of the diverse metabolic strategies of these taxa. Despite this similarity, evidence was found not only for aquifer-specific microbial communities, but also for a common small consortium of prevalent Betaproteobacteria and Gammaproteobacterial OTUs across the localities. This finding implies a core terrestrial deep subsurface community, irrespective of aquifer lithology, that may play an important role in colonising and sustaining microbial habitats in the deep terrestrial subsurface. An in-silico contamination-aware approach to analysing this dataset underscores the importance of downstream methods for assuring that robust conclusions can be reached from deep subsurface-derived sequencing data. Understanding the global panorama of microbial diversity and ecological dynamics in the deep terrestrial subsurface provides a first step towards understanding the role of microbes in global subsurface element and nutrient cycling.

microbiology↗

bioRxiv2019

Gut-innervating nociceptor neurons protect against enteric infection by modulating the microbiota and Peyer’s patch microfold cells

Gut-innervating nociceptor sensory neurons respond to noxious/tissue-damaging stimuli by initiating protective responses and releasing mediators that regulate tissue inflammation, gastrointestinal secretion, and motility. The role of nociceptors in host defense against enteric pathogens is unclear. Here, we found that gut-extrinsic nociceptor neurons are critical in protecting the host against Salmonella typhimurium (STm) infection. Nociceptors responded to STm by releasing the neuropeptide calcitonin gene-related peptide (CGRP). Targeted depletion of Nav1.8 and TRPV1 neurons from gut-extrinsic dorsal root ganglia and vagal ganglia increased STm colonization, invasion, and dissemination. Nociceptors regulated the gut microbiota at homeostasis, specifically segmented filamentous bacteria (SFB) levels in the ileum, which protected against STm by colonization resistance. Nociceptors also regulated the density of microfold epithelial cells in the Peyers patch via CGRP to limit points of entry for STm invasion into host tissues. Understanding how host sensory neurons crosstalk with pathogenic bacteria may impact treatments for enteric infections.\n\nHIGHLIGHTSO_LINav1.8 and TRPV1 nociceptors defend against Salmonella typhimurium (STm) infection\nC_LIO_LINociceptors shape the gut microbiota and SFB levels which resist pathogen colonization\nC_LIO_LINociceptors suppress Peyers patch microfold cell density to limit pathogen invasion\nC_LIO_LINeurons sense STm and release CGRP to modulate microfold cells and host defense\nC_LI

immunology↗

bioRxiv2018

HiAlc Klebsiella pneumonia, one of potential chief culprits of non-alcoholic fatty liver disease: through generation of endogenous ethanol

Non-alcoholic fatty liver disease (NAFLD), a prelude of cirrhosis and hepatocellular carcinoma, is the most common chronic liver disease worldwide. NAFLD has been considerated to be associated with the composition of gut microbiota. However, causal relationship between change of gut microbiome and NAFLD remains unclear. Here we show that Klebsiella pneumoniae was significantly associated with NAFLD through inducing generation of endogenous ethanol. A strain of high alcohol-producing Klebsiella pneumoniae (HiAlc Kpn) was initially isolated from fecal samples of patient with non-alcoholic steatohepatitis (NASH) accompanied with auto-brewery syndrome (ABS). Gavage of HiAlc Kpn was capable of inducing murine model of fatty liver disease (FLD) in which had typical pathological changes of hepatic steatosis and similar liver gene expression profiles to those of alcohol intake in mice. Data derived from germ-free mice by gnotobiotic gavage further demonstrated that the HiAlc Kpn is the major cause of the changes in FLD mice. Furthermore, using proteomic and metabolitic analysis, we found that HiAlc Kpn induced generation of endogenous alcohol through the 2,3-butanediol fermentation pathway. More interestingly, the blood alcohol concentration was elevated in FLD mice induced by HiAlc Kpn after glucose intake. Clinical analysis showed that HiAlc Kpn were observed in up to 60% of patients with NAFLD. Our results suggested that HiAlc Kpn make important contribution to NAFLD, possibly through generation of the endogenous alcohol. Thus, targeting these bacteria might provide a novel therapeutic for clinical treatment of NAFLD.\n\nIn BriefFatty liver disease induced by high alcohol-producing Klebsiella pneumoniae\n\nCompeting Financial Interest StatementThe authors declare no conflicts of interest.

microbiology↗

bioRxiv2018

Intersection of phosphate transport, oxidative stress and TOR signalling in Candida albicans virulence

Phosphate is an essential macronutrient required for cell growth and division. Pho84 is the major high-affinity cell-surface phosphate importer of Saccharomyces cerevisiae and a crucial element in the phosphate homeostatic system of this model yeast. We found that loss of Candida albicans Pho84 attenuated virulence in Drosophila and murine oropharyngeal and disseminated models of invasive infection, and conferred hypersensitivity to neutrophil killing. Susceptibility of cells lacking Pho84 to neutrophil attack depended on reactive oxygen species (ROS): pho84-/- cells were no more susceptible than wild type C. albicans to neutrophils from a patient with chronic granulomatous disease, or to those whose oxidative burst was pharmacologically inhibited or neutralized. pho84-/- mutants hyperactivated oxidative stress signalling. They accumulated intracellular ROS in the absence of extrinsic oxidative stress, in high as well as low ambient phosphate conditions. ROS accumulation correlated with diminished levels of the unique superoxide dismutase Sod3 in pho84-/- cells, while SOD3 overexpression from a conditional promoter substantially restored these cells oxidative stress resistance in vitro. Repression of SOD3 expression sharply increased their oxidative stress hypersensitivity. Neither of these oxidative stress management effects of manipulating SOD3 transcription was observed in PHO84 wild type cells. Sod3 levels were not the only factor driving oxidative stress effects on pho84-/- cells, though, because overexpressing SOD3 did not ameliorate these cells hypersensitivity to neutrophil killing ex vivo, indicating Pho84 has further roles in oxidative stress resistance and virulence. Measurement of cellular metal concentrations demonstrated that diminished Sod3 expression was not due to decreased import of its metal cofactor manganese, as predicted from the function of S. cerevisiae Pho84 as a low-affinity manganese transporter. Instead of a role of Pho84 in metal transport, we found its role in TORC1 activation to impact oxidative stress management: overexpression of the TORC1-activating GTPase Gtr1 relieved the Sod3 deficit and ROS excess in pho84-/- null mutant cells, though it did not suppress their hypersensitivity to neutrophil killing or hyphal growth defect. Pharmacologic inhibition of Pho84 by small molecules including the FDA-approved drug foscarnet also induced ROS accumulation. Inhibiting Pho84 could hence support host defenses by sensitizing C. albicans to oxidative stress.

microbiology↗

bioRxiv2017

A unified web platform for network-based analyses of genomic data

Functional genomics networks are widely used to identify unexpected pathway relationships in large genomic datasets. However, it is challenging to quantitatively compare the signal-to-noise ratio of different networks, the biology they describe, and to identify the optimal network to interpret a particular genetic dataset. Via GeNets users can train a machine-learning model (Quack) to make such comparisons; and they can execute, store, and share analyses of genetic and RNA sequencing datasets.

genomics↗