RESUMEN
Host cells have evolved an intricate regulatory network to fine tune the type-I interferon responses. However, the full picture of this regulatory network remains to be depicted. In this study, we found that knock out of zinc-finger CCHC-type containing protein 8 (ZCCHC8) impairs the replication of influenza A virus (IAV), Sendai virus (Sev), Japanese encephalitis virus (JEV), and vesicular stomatitis virus (VSV). Further investigation unveiled that ZCCHC8 suppresses the type-I interferon responses by targeting the interferon regulatory factor 3 (IRF3) signaling pathway. Mechanistically, ZCCHC8 associates with phosphorylated IRF3 and disrupts the interaction of IRF3 with the co-activator CREB-binding protein (CBP). Additionally, the direct binding of ZCCHC8 with the IFN-stimulated response element (ISRE) impairs the ISRE-binding of IRF3. Our study contributes to the comprehensive understanding for the negative regulatory network of the type-I interferon responses and provides valuable insights for the control of multiple viruses from a host-centric perspective.IMPORTANCEThe innate immune responses serve as the initial line of defense against invading pathogens and harmful substances. Negative regulation of the innate immune responses plays an essential role in avoiding auto-immune diseases and over-activated immune responses. Hence, the comprehensive understanding of the negative regulation network for innate immune responses could provide novel therapeutic insights for the control of viral infections and immune dysfunction. In this study, we report that ZCCHC8 negatively regulates the type-I interferon responses. We illustrate that ZCCHC8 impedes the IRF3-CBP association by interacting with phosphorylated IRF3 and competes with IRF3 for binding to ISRE. Our study demonstrates the role of ZCCHC8 in the replication of multiple RNA viruses and contributes to a deeper understanding of the negative regulation system for the type-I interferon responses.
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Fowl cholera is an infectious disease that affects both poultry and wild birds, characterized by hemorrhagic and septicemic symptoms, caused by Pasteurella multocida (P. multocida), and leading to substantial economic losses in the poultry sector. The development of genetic engineering vaccines against avian P. multocida encountered early-stage challenges due to the limited availability of effective gene editing tools. Presently, NgAgoDM-enhanced homologous recombination stands as a potent technique for achieving efficient gene knockout in avian P. multocida. Hence, this study employed NgAgoDM-enhanced homologous recombination to target and knockout hyaE (239-359aa), hyaD, hexABC, and hexD, denoted as ΔhyaE (239-359aa), ΔhyaD, ΔhexABC, and ΔhexD, respectively. Additionally, we generated a hyaD recovery strain with two point mutations, designated as mhyaD. Thus, this study systematically examined the impact of capsular synthetic gene clusters on the pathogenicity of P. multocida. Moreover, the study demonstrated the critical role of hyaD activity in the virulence of avian P. multocida. This study offers novel insights for enhancing attenuated vaccines further.
Asunto(s)
Infecciones por Pasteurella , Pasteurella multocida , Enfermedades de las Aves de Corral , Pasteurella multocida/genética , Pasteurella multocida/patogenicidad , Animales , Infecciones por Pasteurella/veterinaria , Infecciones por Pasteurella/microbiología , Virulencia/genética , Enfermedades de las Aves de Corral/microbiología , Vacunas Bacterianas/inmunología , Vacunas Bacterianas/genética , Recombinación Homóloga , Vacunas Atenuadas/inmunología , Vacunas Atenuadas/genética , Técnicas de Inactivación de Genes , Pollos/microbiología , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo , Aves/microbiología , Familia de Multigenes , Factores de Virulencia/genética , Aves de Corral/microbiologíaRESUMEN
Two fungal strains (K-2T and S1) were isolated from the deepest ocean sediment of the Challenger Deep located in the Mariana Trench. The internal transcribed spacer (ITS) gene sequences of the isolates K-2T and S1 differed from those of closely related species, such as Talaromyces assiutensis and T. trachyspermus. Phylogenetic analyses based on single and concatenated alignments of the genes, namely ITS, ß-tubulin (benA), calmodulin (cam), and the second-largest subunit fragment of the RNA polymerase II (rpb2) showed that the isolates K-2T and S1 were clustered together with other Talaromyces species, such as T. trachyspermus and T. assiutensis, as evidenced by the position on a terminal branch with high bootstrap support. They could also be distinguished from their closest relatives with valid published names via morphological and physiological characteristics, for example, growth at 4 °C-50 °C with a pH in the range of 1.5-12. Based on their phylogenetic, morphological, and physicochemical properties, the isolates K-2T and S1 represent a novel species in the genus Talaromyces, and the proposed name is Talaromyces sedimenticola sp. nov. The type strain is K-2T (= GDMCC 3.746T = JCM 39451T).
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Ácidos Grasos , Talaromyces , Ácidos Grasos/química , Análisis de Secuencia de ADN , Filogenia , ARN Ribosómico 16S/genética , Técnicas de Tipificación Bacteriana , ADN Bacteriano/genéticaRESUMEN
Simultaneous heterotrophic nitrification and aerobic denitrification (SND) is gaining tremendous attention due to its high efficiency and low cost in water treatment. However, SND on an industrial scale is still immature since effects of coexisting pollutants, for example, heavy metals, on nitrogen removal remains largely unresolved. In this study, a HNAD bacterium (Pseudomonas sp. XF-4) was isolated. It could almost completely remove ammonium and nitrate at pH 5-9 and temperature 20 â-35 â within 10â¯h, and also showed excellently simultaneous nitrification and denitrification efficiency under the coexistence of any two of inorganic nitrogen sources with no intermediate accumulation. XF-4 could rapidly grow again after ammonium vanish when nitrite or nitrate existed. There was no significant effects on nitrification and denitrification when Cd(II) was lower than 10â¯mg/L, and 95â¯% of Cd(II) was removed by XF-4. However, electron carrier and electron transport system activity was inhibited, especially at high concentration of Cd(II). Overall, this study reported a novel strain capable of simultaneous nitrification and denitrification coupled with Cd(II) removal efficiently. The results provided new insights into treatment of groundwater or wastewater contaminated by heavy metals and nitrogen.
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Cadmio , Desnitrificación , Nitrificación , Nitrógeno , Pseudomonas , Contaminantes Químicos del Agua , Cadmio/metabolismo , Pseudomonas/metabolismo , Contaminantes Químicos del Agua/metabolismo , Nitrógeno/metabolismo , Procesos Heterotróficos , Nitratos/metabolismo , Aguas Residuales/microbiología , Aguas Residuales/química , Biodegradación Ambiental , Aerobiosis , Purificación del Agua/métodos , Compuestos de Amonio/metabolismoRESUMEN
Mortierella alpina is popular for lipid production, but the low carbon conversion rate and lipid yield are major obstacles for its economic performance. Here, external addition of organic acids involved in tricarboxylic acid cycle was used to tune carbon flux and improve lipid production. Citrate was determined to be the best organic acid that can be used for enhancing lipid production. By the addition of citrate, the lipid titer and content were approximately 1.24 and 1.34 times higher, respectively. Meanwhile, citrate supplement also promoted the accumulation of succinate, an important value-added platform chemical. Owing to the improved lipid and succinate production through adding citrate, the carbon conversion rate of M. alpina reached up to 52.17%, much higher than that of the control group (14.11%). The addition of citrate could redistribute carbon flux by regulating the expression level of genes related to tricarboxylic acid cycle metabolism. More carbon fluxes flow to lipid and succinate synthesis, which greatly improved the carbon conversion efficiency of M. alpina. This study provides an effective and straightforward strategy with potential economic benefits to improve carbon conversion efficiency in M. alpina.
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Carbono , Ciclo del Ácido Cítrico , Ácido Cítrico , Mortierella , Ácido Succínico , Mortierella/metabolismo , Mortierella/genética , Ácido Succínico/metabolismo , Carbono/metabolismo , Ácido Cítrico/metabolismo , Lípidos/biosíntesis , Metabolismo de los Lípidos , Regulación Fúngica de la Expresión Génica , FermentaciónRESUMEN
Pigeon Newcastle disease (ND) is a serious infectious illness caused by the pigeon Newcastle disease virus (NDV) or Paramyxovirus type 1 (PPMV-1). Genotype VI NDV is a primary factor in ND among Columbiformes (such as pigeons and doves). In a recent study, eight pigeon NDV strains were discovered in various provinces in China. These viruses exhibited mesogenic characteristics based on their MDT and ICPI values. The complete genome sequences of these eight strains showed a 90.40% to 99.19% identity match with reference strains of genotype VI, and a 77.86% to 80.45% identity match with the genotype II vaccine strain. Additionally, analysis of the F gene sequence revealed that these NDV strains were closely associated with sub-genotypes VI.2.2.2, VI.2.1.1.2.1, and VI.2.1.1.2.2. The amino acid sequence at the cleavage site of the F protein indicated virulent characteristics, with the sequences 112KRQKRF117 and 112RRQKRF117 observed. Pigeons infected with these sub-genotype strains had a low survival rate of only 20% to 30%, along with lesions in multiple tissues, highlighting the strong spread and high pathogenicity of these pigeon NDV strains. Molecular epidemiology data from the GenBank database revealed that sub-genotype VI.2.1.1.2.2 strains have been prevalent since 2011. In summary, the findings demonstrate that the prevalence of genotype VI NDV is due to strains from diverse sub-genotypes, with the sub-genotype VI.2.1.1.2.2 strain emerging as the current epidemic strain, highlighting the significance of monitoring pigeon NDV in China.
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Acid mine drainage (AMD) induced by pyrite oxidation is a notorious and serious environmental problem, but the management of AMD in an economical and environmentally friendly way remains challenging. Here, lignin, a natural polymer and abundant waste, was employed as both a bactericide and passivator to prevent AMD formation. The addition of lignin to a mimic AMD formation system inoculated with Acidithiobacillus ferrooxidans at a lignin-to-pyrite weight ratio of 2.5: 10 reduced the combined abiotic and biotic oxidation of pyrite by 68.4 % (based on released SO42-). Morphological characterization of Acidithiobacillus ferrooxidans revealed that lignin could act on the cell surface and impair the cell integrity, disrupting its normal growth and preventing biotic oxidation of pyrite accordingly. Moreover, lignin can be used alone as a passivator to form a coating on the pyrite surface, reducing abiotic oxidation by 71.7 % (based on released SO42-). Through multiple technique analysis, it was proposed that the functional groups on lignin may coordinate with iron ions on pyrite, promoting its deposition on the surface. In addition, the inherent antioxidant activity of lignin may also be actively involved in the abatement of pyrite oxidation via the reduction of iron. Overall, this study offered a "treating waste with waste" strategy for preventing AMD formation at the source and opened a new avenue for the management of AMD.
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Acidithiobacillus , Lignina , Minería , Acidithiobacillus/metabolismo , Hierro , Sulfuros , Oxidación-ReducciónRESUMEN
Marine bacteria influence Earth's environmental dynamics in fundamental ways by controlling the biogeochemistry and productivity of the oceans. However, little is known about the survival strategies of their abundant and rare taxa, especially in polar marine environments. Here, bacterial environmental adaptation, community assembly processes, and co-occurrence patterns between abundant and rare taxa were compared in the Arctic Ocean sediments. Results indicated that the diversity of rare taxa is significantly higher than that of abundant taxa, whereas the distance-decay rate of rare taxa community similarity is over 1.5 times higher than that of abundant taxa. Furthermore, abundant taxa exhibited broader environmental breadth and stronger phylogenetic signals compared to rare taxa. Additionally, the community assembly processes of the abundant taxa were predominantly governed by 81% dispersal limitation, while rare taxa were primarily influenced by 48% heterogeneous selection. The co-occurrence network further revealed the abundant taxa formed a more complex network to enhance their environmental adaptability. This study revealed the differences in environmental responses and community assembly processes between bacterial abundant and rare taxa in polar ocean sediments, providing some valuable insights for understanding their environmental adaptation strategies in marine ecosystems.
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Bacterias , Sedimentos Geológicos , Océanos y Mares , Regiones Árticas , Sedimentos Geológicos/microbiología , Bacterias/clasificación , Bacterias/genética , Bacterias/aislamiento & purificación , Biodiversidad , Filogenia , Ecosistema , Adaptación Fisiológica , Agua de Mar/microbiologíaRESUMEN
Accurately depicting the subsurface mixing of radially injected remediation agents with contaminated plumes remains paramount yet challenging for understanding and simulating reactive transport. To address this, the present research employed the mixing dynamics of a potassium permanganate plume injected into a pre-existing contaminated plume. Through combining colour deconvolution and thresholding, we effectively isolated local mixing values within the Gaussian annular narrow mixing zone from the noise of mixed double-plume images. Key findings revealed increasing injection rate promotes plume mixing while adding xanthan gum to increase fluid viscosity moderates interface mixing, reducing mixing zone width by 25.3% and 37.4% for 100 mg/L and 400 mg/L xanthan gum, respectively. Grain size is pivotal, with a 30% increase in mixing areas observed in coarse-grained sands over medium-grained sands. Balancing sufficient mixing and preventing contaminated plume growth is essential for effective remediation. Injection rates below 5 mL/min may suppress contaminated plume expansion, albeit at the possible cost of protracted remediation durations. For the attainment of optimal remediation, it's imperative to harmonize robust mixing processes with the mitigation of contaminated plume expansion - a balance that adding xanthan gum during the initial injection phase seems poised to achieve (xanthan gum optimized the average mixing index (AMI)). These findings provide valuable insights into groundwater plume mixing, supporting effective remediation strategies.
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Agua Subterránea , Contaminantes Químicos del Agua , Arena , Contaminantes Químicos del Agua/análisisRESUMEN
Microorganisms could be classified as habitat generalists and specialists according to their niche breadth, uncovering their survival strategy is a crucial topic in ecology. Here, differences in environmental adaptation, community assemblies, co-occurrence patterns, and ecological functions between generalists and specialists were explored in the Arctic marine sediments. Compared to specialists, generalists showed lower alpha diversity but stronger environmental adaption, and dispersal limitation contributed more to the community assembly of specialists (74 %) than generalists (46 %). Furthermore, the neutral theory model demonstrated that generalists (m = 0.20) had a higher immigration rate than specialists (m = 0.02), but specialists exhibited more complex co-occurrence patterns than generalists. Our results also found that generalists may play more important roles in C, N, S metabolism but are weaker in carbon fixation and xenobiotic biodegradation and metabolism. This study would broaden our understanding of bacterial generalists' and specialists' survival strategies, and further reveal their ecological functions in marine sediments.
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Ecosistema , Sedimentos Geológicos , Regiones Árticas , Sedimentos Geológicos/química , Bacterias , BiodiversidadRESUMEN
Microplastics have become one of the hot concerns of global marine pollution. In recent years, diversity and abiotic influence factors of plastisphere microbial communities were well documented, but our knowledge of their assembly mechanisms and co-occurrence patterns remains unclear, especially the effects of depth on them. Here, we collected microorganisms on microplastics to investigate how ocean depth affects on microbial diversity, community composition, assembly processes and co-occurrence patterns. Our results indicated that there were similar microbial richness and community compositions but microbial evenness and unique microbes were obviously different in different ocean layers. Our findings also demonstrated that deterministic processes played dominant roles in the assembly of the mesopelagic plastisphere microbial communities, while the bathypelagic microbial community assembly was mainly shaped by stochastic processes. In addition, the co-occurrence networks suggested that the relationships between microorganisms in the mesopelagic layer were more complex and stable than those in the bathypelagic layer. Simultaneously, we also found that Proteobacteria and Actinobacteriota were the most abundant keystones which played important roles in microbial co-occurrence networks at both layers. This study enhanced our understanding of microbial diversity, assembly mechanism, and co-occurrence pattern on plastisphere surfaces, and provided useful insights into microorganisms capable of degrading plastics and microbial remediation.
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Microbiota , Plásticos , Microplásticos , Bacterias , ProteobacteriaRESUMEN
The cost of detoxification and neutralization poses certain challenges to the development of an economically viable lactic acid biorefinery with lignocellulosic biomass as feedstock. Herein, red mud, an alkaline waste, was explored as both a detoxifying agent and a neutralizer. Red mud treatment of lignocellulosic hydrolysate effectively removed the inhibitors generated in dilute acid pretreatment, improving the lactic acid productivity from 1.0 g/L·h-1 to 1.9 g/L·h-1 in later fermentation. In addition, red mud could replace CaCO3 as a neutralizer in lactic acid fermentation, which in turn enabled simultaneous bioleaching of valuable metals (Sc, Y, Nd, and Al) from red mud. The neutralization of alkali in red mud by acids retained in lignocellulosic hydrolysate and lactic acid produced from fermentation led to effective dealkalization, rendering a maximum alkali removal efficiency of 92.2 %. Overall, this study offered a win-win strategy for the valorization of both lignocellulosic biomass and red mud.
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Ácido Láctico , Lignina , Lignina/química , Fermentación , Óxido de Aluminio/química , Biomasa , Hidrólisis , Residuos IndustrialesRESUMEN
Ferroptosis is a novel form of cell death caused by the accumulation of lipid peroxides in an iron-dependent manner. However, the precise mechanism underlying the exploitation of ferroptosis by influenza A viruses (IAV) remains unclear. The results demonstrate that IAV promotes its own replication through ferritinophagy by sensitizing cells to ferroptosis, with hemagglutinin identified as a key trigger in this process. Hemagglutinin interacts with autophagic receptors nuclear receptor coactivator 4 (NCOA4) and tax1-binding protein 1 (TAX1BP1), facilitating the formation of ferritin-NCOA4 condensates and inducing ferritinophagy. Further investigation shows that hemagglutinin-induced ferritinophagy causes cellular lipid peroxidation, inhibits aggregation of mitochondrial antiviral signaling protein (MAVS), and suppresses the type I interferon response, thereby contributing to viral replication. Collectively, a novel mechanism by which IAV hemagglutinin induces ferritinophagy resulting in cellular lipid peroxidation, consequently impairing MAVS-mediated antiviral immunity, is revealed.
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Influenza A virus (IAV) causes annual epidemics and occasional pandemics, resulting in significant economic losses and numerous fatalities. Current vaccines, typically administered through injection, provide limited protection due to the frequent antigenic shift and drift of IAV strains. Therefore, the development of alternative broad-spectrum vaccine strategies is imperative. Lactic acid bacteria (LAB) represent promising candidates for vaccine engineering due to their low cost, high safety profile, and suitability for oral administration. In this study, we identified a strain of Lactobacillus plantarum (Lp) that is resistant to acid and bile salts and capable of colonizing the intestines of mice. Subsequently, we employed the RecE/T gene editing system to integrate headless hemagglutinins (mini-HA) into the genome of Lp, generating Lp-mini-HA-SP. Remarkably, immunization with Lp-mini-HA-SP elicited serum IgG antibody responses and conferred immune protection against H9N2 and H1N1 influenza virus challenges. Collectively, our findings offer a novel approach for the development of orally administered IAV vaccines and hold significant potential for future drug development endeavors.
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Subtipo H1N1 del Virus de la Influenza A , Subtipo H9N2 del Virus de la Influenza A , Vacunas contra la Influenza , Lactobacillus plantarum , Infecciones por Orthomyxoviridae , Vacunas Sintéticas , Lactobacillus plantarum/genética , Lactobacillus plantarum/inmunología , Animales , Subtipo H9N2 del Virus de la Influenza A/inmunología , Subtipo H9N2 del Virus de la Influenza A/genética , Subtipo H1N1 del Virus de la Influenza A/inmunología , Ratones , Vacunas contra la Influenza/inmunología , Infecciones por Orthomyxoviridae/prevención & control , Infecciones por Orthomyxoviridae/inmunología , Vacunas Sintéticas/inmunología , Anticuerpos Antivirales/sangre , Anticuerpos Antivirales/inmunología , Femenino , Ratones Endogámicos BALB CRESUMEN
Macroautophagy/autophagy plays a crucial role in inhibiting viral replication and regulating the host's immune response. The autophagy receptor SQSTM1/p62 (sequestosome 1) restricts viral replication by directing specific viral proteins to phagophores for degradation. In this study, we investigate the reciprocal relationship between Zika virus (ZIKV) and selective autophagy mediated by SQSTM1/p62. We show that NS2B3 protease encoded by ZIKV cleaves human SQSTM1/p62 at arginine 265 (R265). This cleavage also occurs with endogenous SQSTM1 in ZIKV-infected cells. Furthermore, overexpression of SQSTM1 inhibits ZIKV replication in A549 cells, while its absence increases viral titer. We have also shown that SQSTM1 impedes ZIKV replication by interacting with NS3 and NS5 and directing them to autophagic degradation, and that NS2B3-mediated cleavage could potentially alter this antiviral function of SQSTM1. Taken together, our study highlights the role of SQSTM1-mediated selective autophagy in the host's antiviral defense against ZIKV and uncovers potential viral evasion strategies that exploit the host's autophagic machinery to ensure successful infection.Abbreviation: Cas9: CRISPR-associated protein 9; Co-IP: co-immunoprecipitation; CRISPR: clustered regularly interspaced short palindromic repeats; DENV: dengue virus; GFP: green fluorescent protein; IFA: indirect immunofluorescence assay; KIR: KEAP1-interacting region; KO: knockout; LIR: MAP1LC3/LC3-interacting region; mAb: monoclonal antibody; NBR1: NBR1 autophagy cargo receptor; OPTN: optineurin; pAb: polyclonal antibody; PB1: Phox/BEM1 domain; R265A, a SQSTM1 construct with the arginine (R) residue at position 265 replaced with glutamic acid (A); SQSTM1: sequestosome 1; SQSTM1-C, C-terminal fragment of SQSTM1; SQSTM1-N, N-terminal fragment of SQSTM1; SVV: Seneca Valley virus; TAX1BP1: Tax1 binding protein 1; TBD: TRAF6-binding domain; TCID50: 50% tissue culture infective dose; UBA: ubiquitin-associated domain; Ub: ubiquitin; WT: wild type; ZIKV: Zika virus; ZZ: ZZ-type zinc finger domain.
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Among the enzymes derived from fungus that act on polysaccharides, lytic polysaccharide monooxygenase (LPMOs) has emerged as a new member with complex reaction mechanisms and high efficiency in dealing with recalcitrant crystalline polysaccharides. This study reported the characteristics, structure, and biochemical properties of a novel LPMO from Talaromyces sedimenticola (namely MaLPMO9K) obtained from the Mariana Trench. MaLPMO9K was a multi-domain protein combined with main body and a carbohydrate-binding module. It was heterologously expressed in E. coli for analyzing peroxidase activity in reactions with the substrate 2,6-DMP, where H2O2 serves as a co-substrate. Optimal peroxidase activity for MaLPMO9K was observed at pH 8 and 25 °C, achieving the best Vmax value of 265.2 U·g-1. In addition, MaLPMO9K also demonstrated the ability to treat cellulose derivatives, and cellobiose substrates without the presence of reducing agents.
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Celulosa , Oxigenasas de Función Mixta , Oxidación-Reducción , Oxigenasas de Función Mixta/metabolismo , Oxigenasas de Función Mixta/química , Celulosa/metabolismo , Celulosa/química , Talaromyces/enzimología , Especificidad por Sustrato , Concentración de Iones de Hidrógeno , Sustancias Reductoras/química , Polisacáridos/metabolismo , Polisacáridos/química , Peróxido de Hidrógeno/metabolismo , Cinética , Proteínas Fúngicas/metabolismo , Proteínas Fúngicas/química , Organismos AcuáticosRESUMEN
Low pH eliminated the jarosite accumulation and improved the interfacial reaction rate during the bioleaching process. However, high acidity tends to make environments less hospitable, even for organisms that live in extreme places, so a great challenge existed for bioleaching at low pH conditions. This study demonstrated that the adaption and bioleaching ability of Leptospirillum ferriphilum could be improved after the long-term adaptive evolution of the community under acidity conditions. It was found that the acidity-adapted strain showed robust ferrous iron oxidation activity in wider pH, high concentration of ferrous iron, and lower temperature. Although the enhancement for heavy metal tolerance was limited, the resistance for MgSO4, Na2SO4, and organic matter was stimulative. More importantly, both pyrite and printed circuit board bioleaching revealed the higher bioleaching ability of the acid-resistant strain. These adaptation and bioleaching details provided an available approach for the improvement of bioleaching techniques.(AU)