Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 30
Filter
1.
ISME J ; 18(1)2024 Jan 08.
Article in English | MEDLINE | ID: mdl-38952008

ABSTRACT

Microbial interactions impact the functioning of microbial communities. However, microbial interactions within host-associated communities remain poorly understood. Here, we report that the beneficiary rhizobacterium Niallia sp. RD1 requires the helper Pseudomonas putida H3 for bacterial growth and beneficial interactions with the plant host. In the absence of the helper H3 strain, the Niallia sp. RD1 strain exhibited weak respiration and elongated cell morphology without forming bacterial colonies. A transposon mutant of H3 in a gene encoding succinate-semialdehyde dehydrogenase displayed much attenuated support of RD1 colony formation. Through the subsequent addition of succinate to the media, we found that succinate serves as a public good that supports RD1 growth. Comparative genome analysis highlighted that RD1 lacked the gene for sufficient succinate, suggesting its evolution as a beneficiary of succinate biosynthesis. The syntrophic interaction between RD1 and H3 efficiently protected tomato plants from bacterial wilt and promoted tomato growth. The addition of succinate to the medium restored complex II-dependent respiration in RD1 and facilitated the cultivation of various bacterial isolates from the rhizosphere. Taken together, we delineate energy auxotrophic beneficiaries ubiquitous in the microbial community, and these beneficiaries could benefit host plants with the aid of helpers in the rhizosphere.


Subject(s)
Rhizosphere , Solanum lycopersicum , Succinic Acid , Solanum lycopersicum/microbiology , Succinic Acid/metabolism , Microbial Interactions , Soil Microbiology , Pseudomonas putida/genetics , Pseudomonas putida/metabolism , Pseudomonas putida/growth & development
2.
Plant Pathol J ; 40(3): 251-260, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38835296

ABSTRACT

Flavobacterium is a genus within the phylum Bacteroidota that remains relatively unexplored. Recent analyses of plant microbiota have identified the phylum Bacteroidota as a major bacterial group in the plant rhizosphere. While Flavobacterium species within the phylum Bacteroidota have been recognized as pathogens in the aquatic habitats, microbiome analysis and the characterization of novel Flavobacterium species have indicated the great diversity and potential of their presence in various environments. Many Flavobacterium species have positively contribute to plant health and development, including growth promotion, disease control, and tolerance to abiotic stress. Despite the well-described beneficial interactions of the Flavobacterium species with plants, the molecular mechanisms and bacterial determinants underlying these interactions remain unclear. To broaden our understanding of the genus Flavobacterium's role in plant health, we review the recent studies focusing on their ecological niche, functional roles, and determinants in plant-beneficial interactions. Additionally, this review discusses putative mechanisms explaining the interactions between plants and Flavobacterium. We have also introduced the importance of future research on Flavobacterium spp. and its potential applications in agriculture.

3.
Plant Pathol J ; 39(5): 417-429, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37817490

ABSTRACT

Ralstonia solanacearum species complex (RSSC) is a soil borne plant pathogen causing bacterial wilt on various important crops, including Solanaceae plants. The bacterial pathogens within the RSSC produce exopolysaccharide (EPS), a highly complicated nitrogen-containing heteropolymeric polysaccharide, as a major virulence factor. However, the biosynthetic pathway of the EPS in the RSSC has not been fully characterized. To identify genes in EPS production beyond the EPS biosynthetic gene operon, we selected the EPS-defective mutants of R. pseudosolanacearum strain SL341 from Tn5-inserted mutant pool. Among several EPS-defective mutants, we identified a mutant, SL341P4, with a Tn5-insertion in a gene encoding a putative NDP-sugar epimerase, a putative membrane protein with sugar-modifying moiety, in a reverse orientation to EPS biosynthesis gene cluster. This protein showed similar to other NDP-sugar epimerases involved in EPS biosynthesis in many phytopathogens. Mutation of the NDP-sugar epimerase gene reduced EPS production and biofilm formation in R. pseudosolanacearum. Additionally, the SL341P4 mutant exhibited reduced disease severity and incidence of bacterial wilt in tomato plants compared to the wild-type SL341 without alteration of bacterial multiplication. These results indicate that the NDP-sugar epimerase gene is required for EPS production and bacterial virulence in R. pseudosolanacearum.

4.
Toxins (Basel) ; 13(11)2021 10 20.
Article in English | MEDLINE | ID: mdl-34822523

ABSTRACT

Retinoic acid (RA) is one of the factors crucial for cell growth, differentiation, and embryogenesis; it interacts with the retinoic acid receptor and retinoic acid X receptor to eventually regulate target gene expression in chordates. RA is transformed from retinaldehyde via oxidization by retinaldehyde dehydrogenase (RALDH), which belongs to the family of oxidoreductases. Several chemicals, including disulphiram, diethylaminobenzaldehyde, and SB-210661, can effectively inhibit RALDH activity, potentially causing reproductive and developmental toxicity. The modes of action can be sequentially explained based on the molecular initiating event toward key events, and finally the adverse outcomes. Adverse outcome pathway (AOP) is a conceptual and theoretical framework that describes the sequential chain of casually liked events at different biological levels from molecular events to adverse effects. In the present review, we discussed a recently registered AOP (AOP297; inhibition of retinaldehyde dehydrogenase leads to population decline) to explain and support the weight of evidence for RALDH inhibition-related developmental toxicity using the existing knowledge.


Subject(s)
Embryo, Mammalian/metabolism , Embryo, Nonmammalian/metabolism , Retinal Dehydrogenase/antagonists & inhibitors , Tretinoin/antagonists & inhibitors , Adverse Outcome Pathways , Animals , Cell Differentiation , Embryo, Mammalian/embryology , Embryo, Nonmammalian/embryology , Embryonic Development , Fishes , Gene Expression Regulation, Developmental , Mice , Rabbits , Rats
5.
Int J Syst Evol Microbiol ; 71(10)2021 Oct.
Article in English | MEDLINE | ID: mdl-34596509

ABSTRACT

A bacterial strain, designated TCH3-2T, was isolated from the rhizosphere of tomato plant grown at Dong-A University Agricultural Experiment Station, Republic of Korea. The strain was Gram-stain-negative, obligate aerobic, orange yellow-coloured, motile by gliding and short rod-shaped. Strain TCH3-2 T only grew on 1/2 tryptic soy agar and Luria-Bertani agar among the media tested, with optimum growth at 28 °C and pH 7. Salt of 1 % NaCl was necessary to support the growth of TCH3-2T. Strain TCH3-2T produced flexirubin-type pigments. The predominant cellular fatty acids were iso-C15 : 0 (55.6 %), iso-C17 : 0 3-OH (17.9 %), summed feature 9 (comprising C16 : 0 10-methyl and/or iso-C17 : 1 ω9c; 10.5 %), iso-C15 : 0 3-OH (4.8 %) and anteiso-C15 : 0 (2.3 %). The major menaquinone was menaquinone-6 and the major polar lipids were phosphatidylethanolamine, five unknown aminolipids and three unknown lipids. Phylogenetic analysis based on 16S rRNA sequences indicated that TCH3-2T was closely related to Flavobacterium ummariense DS-12T (95.16 %), Flavobacterium marinum SW105T (95.14 %) and Flavobacterium viscosus YIM 102796T (94.54 %). The draft genome of TCH3-2T comprised ca. 2.8 Mb with a G+C content of 34.61 mol%. The average nucleotide identity and digital DNA-DNA hybridization values between TCH3-2T and closely related Flavobacterium species showed that it belongs to a distinct species. Furthermore, the results of morphological, physiological and biochemical tests allowed further phenotypic differentiation of TCH3-2T from its closest relatives. Thus, chemotaxonomic characteristics together with phylogenetic affiliation illustrate that TCH3-2T represents a novel species of the genus Flavobacterium, for which the name Flavobacterium dauae sp. nov. (type strain TCH3-2T=KACC 19054T=JCM 34025T) is proposed.


Subject(s)
Flavobacterium , Phylogeny , Rhizosphere , Soil Microbiology , Solanum lycopersicum , Bacterial Typing Techniques , Base Composition , DNA, Bacterial/genetics , Fatty Acids/chemistry , Flavobacterium/classification , Flavobacterium/isolation & purification , Solanum lycopersicum/microbiology , Nucleic Acid Hybridization , Phospholipids/chemistry , Pigmentation , RNA, Ribosomal, 16S/genetics , Republic of Korea , Sequence Analysis, DNA , Vitamin K 2/analogs & derivatives , Vitamin K 2/chemistry
6.
Front Plant Sci ; 12: 599742, 2021.
Article in English | MEDLINE | ID: mdl-33613596

ABSTRACT

Previously, algae were recognized as small prokaryotic and eukaryotic organisms found only in aquatic habitats. However, according to a recent paradigm shift, algae are considered ubiquitous organisms, occurring in plant tissues as well as in soil. Accumulating evidence suggests that algae represent a member of the plant microbiome. New results indicate that plants respond to algae and activate related downstream signaling pathways. Application of algae has beneficial effects on plant health, such as plant growth promotion and disease control. Although accumulating evidence suggests that secreted compounds and cell wall components of algae induce physiological and structural changes in plants that protect against biotic and abiotic stresses, knowledge of the underlying mechanisms and algal determinants is limited. In this review, we discuss recent studies on this topic, and highlight the bioprotectant and biostimulant roles of algae as a new member of the plant beneficial microbiome for crop improvement.

7.
ISME J ; 15(1): 330-347, 2021 01.
Article in English | MEDLINE | ID: mdl-33028974

ABSTRACT

Enrichment of protective microbiota in the rhizosphere facilitates disease suppression. However, how the disruption of protective rhizobacteria affects disease suppression is largely unknown. Here, we analyzed the rhizosphere microbial community of a healthy and diseased tomato plant grown <30-cm apart in a greenhouse at three different locations in South Korea. The abundance of Gram-positive Actinobacteria and Firmicutes phyla was lower in diseased rhizosphere soil (DRS) than in healthy rhizosphere soil (HRS) without changes in the causative Ralstonia solanacearum population. Artificial disruption of Gram-positive bacteria in HRS using 500-µg/mL vancomycin increased bacterial wilt occurrence in tomato. To identify HRS-specific and plant-protective Gram-positive bacteria species, Brevibacterium frigoritolerans HRS1, Bacillus niacini HRS2, Solibacillus silvestris HRS3, and Bacillus luciferensis HRS4 were selected from among 326 heat-stable culturable bacteria isolates. These four strains did not directly antagonize R. solanacearum but activated plant immunity. A synthetic community comprising these four strains displayed greater immune activation against R. solanacearum and extended plant protection by 4 more days in comparison with each individual strain. Overall, our results demonstrate for the first time that dysbiosis of the protective Gram-positive bacterial community in DRS promotes the incidence of disease.


Subject(s)
Actinobacteria , Ralstonia solanacearum , Solanum lycopersicum , Actinobacteria/genetics , Bacillus , Bacteria/genetics , Firmicutes/genetics , Incidence , Planococcaceae , Plant Diseases , Ralstonia solanacearum/genetics , Rhizosphere , Soil Microbiology
8.
Plant Signal Behav ; 15(6): 1763005, 2020 06 02.
Article in English | MEDLINE | ID: mdl-32408798

ABSTRACT

Plant tissues naturally senesce over time. Attempts to improve plant robustness and increase longevity have involved genetic modification, application of synthetic chemicals, and use of beneficial microbes. Recently, culture supernatant from a microalga Chlorella fusca was found to prime innate immunity against Pseudomonas syringae in Arabidopsis thaliana. However, the capacity of Chlorella culture supernatants to prevent or delay aging in higher plants has not been elucidated. In this study, roots of the ornamental flowering plant Erinus alpinus L. were drenched with cell-free supernatants from three Chlorella species. Flower and leaf senescence in E. alpinus was significantly reduced and delayed with all three Chlorella supernatants. Investigations of the mode of action underlying delayed senescence showed that the Chlorella supernatants did not act as a chemical trigger to elicit plant immunity or as a growth-promoting fertilizer in E. alpinus. The mechanisms underlying the anti-aging effects remain undetermined, and several possible hypotheses are discussed. Several Chlorella species are industrially cultivated, and disposal of cell-free supernatant can be economically and environmentally challenging. This study provides a novel method for extending plant lifespan through use of Chlorella supernatant and discusses the potential of using industrial waste supernatants in agriculture and horticulture to reduce reliance on chemical pesticides and genetic modification.


Subject(s)
Chlorella/metabolism , Flowers/metabolism , Plant Leaves/metabolism , Cellular Senescence/physiology , Chlorella/physiology , Flowers/physiology , Plant Leaves/physiology
9.
Plant J ; 102(4): 761-778, 2020 05.
Article in English | MEDLINE | ID: mdl-31869481

ABSTRACT

Biological control agents including microbes and their products have been studied as sustainable crop protection strategies. Although aquatic microalgae have been recently introduced as a biological control agent, the underlying molecular mechanisms are largely unknown. The aim of the present study was to investigate the molecular mechanisms underlying biological control by microalga Chlorella fusca. Foliar application of C. fusca elicits induced resistance in Arabidopsis thaliana against Pseudomonas syringae pv. tomato DC3000 that activates plant immunity rather than direct antagonism. To understand the basis of C. fusca-triggered induced resistance at the transcriptional level, we conducted RNA sequencing (RNA-seq) analysis. RNA-seq data showed that, upon pathogen inoculation, C. fusca treatment primed the expression of cysteine-rich receptor-like kinases, WRKY transcription factor genes, and salicylic acid and jasmonic acid signalling-related genes. Intriguingly, the application of C. fusca primed pathogen-associated molecular pattern -triggered immunity, characterized by reactive oxygen species burst and callose deposition, upon flagellin 22 treatment. The attempts to find C. fusca determinants allowed us to identify d-lactic acid secreted in the supernatant of C. fusca as a defence priming agent. This is the first report of the mechanism of innate immune activation by aquatic microalga Chlorella in higher plants.


Subject(s)
Arabidopsis/immunology , Chlorella/immunology , Lactic Acid/metabolism , Plant Diseases/immunology , Plant Growth Regulators/metabolism , Pseudomonas syringae/immunology , Arabidopsis/genetics , Arabidopsis/microbiology , Chlorella/genetics , Chlorella/microbiology , Cyclopentanes/metabolism , Flagellin/metabolism , Glucans/metabolism , Oxylipins/metabolism , Plant Diseases/microbiology , Plant Immunity , Reactive Oxygen Species/metabolism , Salicylic Acid/metabolism
10.
J Virol ; 93(17)2019 09 01.
Article in English | MEDLINE | ID: mdl-31167918

ABSTRACT

Combating influenza is one of the perennial global public health issues to be managed. Antiviral drugs are useful for the treatment of influenza in the absence of an appropriate vaccine. However, the appearance of resistant strains necessitates a constant search for new drugs. In this study, we investigated novel anti-influenza drug candidates using in vitro and in vivo assays. We identified anti-influenza hit compounds using a high-throughput screening method with a green fluorescent protein-tagged recombinant influenza virus. Through subsequent analyses of their cytotoxicity and pharmacokinetic properties, one candidate (IY7640) was selected for further evaluation. In a replication kinetics analysis, IY7640 showed greater inhibitory effects during the early phase of viral infection than the viral neuraminidase inhibitor oseltamivir. In addition, we observed that hemagglutinin (HA)-mediated membrane fusion was inhibited by IY7640 treatment, indicating that the HA stalk region, which is highly conserved across various (sub)types of influenza viruses, may be the molecular target of IY7640. In an escape mutant analysis in cells, amino acid mutations were identified at the HA stalk region of the 2009 pandemic H1N1 (pH1N1) virus. Even though the in vivo efficacy of IY7640 did not reach complete protection in a lethal challenge study in mice, these results suggest that IY7640 has potential to be developed as a new type of anti-influenza drug.IMPORTANCE Anti-influenza drugs with broad-spectrum efficacy against antigenically diverse influenza viruses can be highly useful when no vaccines are available. To develop new anti-influenza drugs, we screened a number of small molecules and identified a strong candidate, IY7640. When added at the time of or after influenza virus infection, IY7640 was observed to successfully inhibit or reduce viral replication in cells. We subsequently discovered that IY7640 targets the stalk region of the influenza HA protein, which exhibits a relatively high degree of amino acid sequence conservation across various (sub)types of influenza viruses. Furthermore, IY7640 was observed to block HA-mediated membrane fusion of H1N1, H3N2, and influenza B viruses in cells. Although it appears less effective against strains other than H1N1 subtype viruses in a challenge study in mice, we suggest that the small molecule IY7640 has potential to be optimized as a new anti-influenza drug.


Subject(s)
Hemagglutinin Glycoproteins, Influenza Virus/metabolism , Influenza A Virus, H1N1 Subtype/physiology , Influenza Vaccines/administration & dosage , Orthomyxoviridae Infections/prevention & control , Small Molecule Libraries/administration & dosage , Animals , Chlorocebus aethiops , Disease Models, Animal , Dogs , Female , Hemagglutinin Glycoproteins, Influenza Virus/genetics , Humans , Influenza A Virus, H1N1 Subtype/drug effects , Influenza A Virus, H1N1 Subtype/genetics , Influenza Vaccines/pharmacology , Madin Darby Canine Kidney Cells , Membrane Fusion/drug effects , Mice , Mutation , Orthomyxoviridae Infections/immunology , Small Molecule Libraries/pharmacology , Vero Cells , Virus Replication/drug effects
11.
Genes Genomics ; 41(7): 811-829, 2019 07.
Article in English | MEDLINE | ID: mdl-30900192

ABSTRACT

BACKGROUND: Leaf morphology influences plant growth and productivity and is controlled by genetic and environmental cues. The various morphotypes of Brassica rapa provide an excellent resource for genetic and molecular studies of morphological traits. OBJECTIVE: This study aimed to identify genes regulating leaf morphology using segregating B. rapa p F2 population. METHODS: Phenotyping and transcriptomic analyses were performed on an F2 population derived from a cross between Rapid cycling B. rapa (RCBr) and B. rapa ssp. penkinensis, inbred line Kenshin. Analyses focused on four target traits: lamina (leaf) length (LL), lamina width (LW), petiole length (PL), and leaf margin (LM). RESULTS: All four traits were controlled by multiple QTLs, and expression of 466 and 602 genes showed positive and negative correlation with leaf phenotypes, respectively. From this microarray analysis, large numbers of genes were putatively identified as leaf morphology-related genes. The Gene Ontology (GO) category containing the highest number of differentially expressed genes (DEGs) was "phytohormones". The sets of genes enriched in the four leaf phenotypes did not overlap, indicating that each phenotype was regulated by a different set of genes. The expression of BrAS2, BrAN3, BrCYCB1;2, BrCYCB2;1,4, BrCYCB3;1, CrCYCBD3;2, BrULT1, and BrANT seemed to be related to leaf size traits (LL and LW), whereas BrCUC1, BrCUC2, and BrCUC3 expression for LM trait. CONCLUSION: An analysis integrating the results of the current study with previously published data revealed that Kenshin alleles largely determined LL and LW but LM resulted from RCBr alleles. Genes identified in this study could be used to develop molecular markers for use in Brassica breeding projects and for the dissection of gene function.


Subject(s)
Brassica/genetics , Plant Leaves/anatomy & histology , Quantitative Trait Loci , Transcriptome , Brassica/anatomy & histology , Inbreeding , Phenotype , Plant Leaves/genetics , Plant Proteins/genetics , Plant Proteins/metabolism
12.
New Phytol ; 220(3): 684-691, 2018 11.
Article in English | MEDLINE | ID: mdl-29266296

ABSTRACT

Plants emit a plethora of volatile organic compounds in response to biotic and abiotic stresses. These compounds act as infochemicals for ecological communication in the phytobiome. This study reviews the role of microbe-induced plant volatiles (MIPVs) in plant-microbe interactions. MIPVs are affected by the taxonomic position of the microbe, the identity of the plant and the type of interaction. Plants also emit exclusive blends of volatiles in response to nonhost and host interactions, as well as to beneficial microbes and necrotrophic/biotrophic pathogens. These MIPVs directly inhibit pathogen growth and indirectly promote resistance/susceptibility to subsequent plant pathogen attack. Viruses and phloem-limiting bacteria modify plant volatiles to attract insect vectors. Susceptible plants can respond to MIPVs from resistant plants and become resistant. Recent advances in our understanding of the molecular mechanisms of MIPV synthesis in plants and how plant pathogen effectors manipulate their biosynthesis are discussed. This knowledge will help broaden our understanding of plant-microbe interactions and should facilitate the development of new emerging techniques for sustainable plant disease management.


Subject(s)
Bacteria/metabolism , Fungi/metabolism , Plants/metabolism , Plants/microbiology , Volatile Organic Compounds/metabolism , Signal Transduction , Volatile Organic Compounds/chemistry
13.
Epilepsy Behav ; 74: 94-98, 2017 09.
Article in English | MEDLINE | ID: mdl-28732261

ABSTRACT

PURPOSE: Epilepsy is a concealable stigmatizing condition. We investigated the factors predicting disclosure management behavior in Korean adults with newly diagnosed epilepsy. METHODS: This longitudinal multicenter study included Korean adults with newly diagnosed epilepsy. Using statistical analyses, we determined at the end of a 1-year follow-up whether Disclosure Management Scale (DMS) scores were predicted by demographic, clinical, and psychosocial variables, including felt stigma, stress coping style, personality traits, social support, and experienced discrimination from society. RESULTS: Of a total of 121 participants, 69% reported that they often or sometimes kept their diagnosis a secret from others and rarely or never talked to others about their epilepsy. The average DMS score was 5.8 (SD=2.9, range 0-11). In univariate analyses, DMS scores were significantly associated with an emotion-focused coping style (r=0.320, p<0.001), social support (r=-0.185, p<0.05), and experienced discrimination (p<0.05). Emotion-focused coping was the only independent predictor of a higher DMS score. Felt stigma, personality traits, and seizure freedom were not related to the DMS score. CONCLUSIONS: Two-thirds of Korean adults with newly diagnosed epilepsy often or sometimes keep their epilepsy a secret. Emotion-focused coping is the most important predictor of concealment of epilepsy diagnosis at the end of a 1-year follow-up, although social support and episodes of experienced discrimination are also associated with disclosure management strategies.


Subject(s)
Adaptation, Psychological/physiology , Epilepsy/psychology , Social Stigma , Social Support , Truth Disclosure , Adult , Emotions/physiology , Epilepsy/diagnosis , Female , Follow-Up Studies , Humans , Longitudinal Studies , Male , Middle Aged , Personality , Republic of Korea , Stress, Psychological/psychology , Young Adult
14.
Trends Plant Sci ; 22(5): 357-360, 2017 05.
Article in English | MEDLINE | ID: mdl-28366543

ABSTRACT

Circular RNAs (circ-RNAs), a novel class of noncoding RNAs, are a popular topic in animal research because they have potential as post-transcriptional regulators and diagnostic markers. Research in plants is only now emerging, but indicates that circ-RNAs could also be a crucial class of noncoding regulators.


Subject(s)
RNA Splicing/genetics , RNA, Plant/genetics , RNA/genetics , Gene Expression Regulation , MicroRNAs/genetics , RNA, Circular , RNA, Untranslated/genetics
15.
Epilepsy Behav ; 54: 1-6, 2016 Jan.
Article in English | MEDLINE | ID: mdl-26610094

ABSTRACT

PURPOSE: We evaluated the course of perceived stigma and the factors associated with perceived stigma over the first year in newly diagnosed people with epilepsy (PWE). METHODS: We recruited newly diagnosed PWE from 12 tertiary hospitals in Korea. The perceived stigma of epilepsy was assessed using the Stigma Scale at baseline and one year later. At the time of diagnosis, demographic, clinical seizure-related, and psychological data were collected. The predictive factors for perceived stigma over one year were analyzed using logistic regression analyses. RESULTS: Two hundred eighteen newly diagnosed PWE were included at baseline, and 153 completed the study. The percentage of participants who felt stigmatized decreased from 30.7% at the time of diagnosis to 17.6% at the end of follow-up. Introverted personality and a high level of anxiety were independent factors contributing to stigma at the time of epilepsy diagnosis. At the one-year follow-up, introverted personality and lower economic status were predictive of the development of perceived stigma. CONCLUSION: Introverted personality was an important factor contributing to the development of perceived stigma at the time of diagnosis and at one year after diagnosis. In addition, a high level of anxiety and a low economic status were independently related to feelings of stigma at baseline and at one year after diagnosis, respectively. There may be a decrease in the perception of stigma over one year in newly diagnosed PWE.


Subject(s)
Epilepsy/psychology , Personality , Seizures/psychology , Social Stigma , Stereotyping , Adult , Female , Humans , Longitudinal Studies , Male , Middle Aged , Personality Tests , Republic of Korea , Young Adult
16.
PLoS One ; 9(7): e101325, 2014.
Article in English | MEDLINE | ID: mdl-24992479

ABSTRACT

Antiviral drugs are being used for therapeutic purposes against influenza illness in humans. However, antiviral-resistant variants often nullify the effectiveness of antivirals. Combined medications, as seen in the treatment of cancers and other infectious diseases, have been suggested as an option for the control of antiviral-resistant influenza viruses. Here, we evaluated the therapeutic value of combination therapy against oseltamivir-resistant 2009 pandemic influenza H1N1 virus infection in DBA/2 mice. Mice were treated for five days with favipiravir and peramivir starting 4 hours after lethal challenge. Compared with either monotherapy, combination therapy saved more mice from viral lethality and resulted in increased antiviral efficacy in the lungs of infected mice. Furthermore, the synergism between the two antivirals, which was consistent with the survival outcomes of combination therapy, indicated that favipiravir could serve as a critical agent of combination therapy for the control of oseltamivir-resistant strains. Our results provide new insight into the feasibility of favipiravir in combination therapy against oseltamivir-resistant influenza virus infection.


Subject(s)
Amides/pharmacology , Antiviral Agents/pharmacology , Cyclopentanes/pharmacology , Guanidines/pharmacology , Influenza A Virus, H1N1 Subtype/drug effects , Pyrazines/pharmacology , Acids, Carbocyclic , Amides/therapeutic use , Animals , Antiviral Agents/therapeutic use , Body Weight/drug effects , Cyclopentanes/therapeutic use , Dogs , Drug Resistance, Viral/drug effects , Drug Synergism , Drug Therapy, Combination , Female , Guanidines/therapeutic use , Lung/virology , Madin Darby Canine Kidney Cells , Mice , Mice, Inbred DBA , Orthomyxoviridae Infections/drug therapy , Orthomyxoviridae Infections/mortality , Oseltamivir/pharmacology , Pyrazines/therapeutic use , Survival Rate
17.
Biochem Biophys Res Commun ; 449(1): 19-25, 2014 Jun 20.
Article in English | MEDLINE | ID: mdl-24802398

ABSTRACT

By nature of their segmented RNA genome, influenza A viruses (IAVs) have the potential to generate variants through a reassortment process. The influenza nonstructural (NS) gene is critical for a virus to counteract the antiviral responses of the host. Therefore, a newly acquired NS segment potentially determines the replication efficiency of the reassortant virus in a range of different hosts. In addition, the C-terminal PDZ-binding motif (PBM) has been suggested as a pathogenic determinant of IAVs. To gauge the pandemic potential from human and avian IAV reassortment, we assessed the replication properties of NS-reassorted viruses in cultured cells and in the lungs of mice and determined their transmissibility in guinea pigs. Compared with the recombinant A/Korea/01/2009 virus (rK09; 2009 pandemic H1N1 strain), the rK09/VN:NS virus, in which the NS gene was adopted from the A/Vietnam/1203/2004 virus (a human isolate of the highly pathogenic avian influenza H5N1 virus strains), exhibited attenuated virulence and reduced transmissibility. However, the rK09/VN:NS-PBM virus, harboring the PBM in the C-terminus of the NS1 protein, recovered the attenuated virulence of the rK09/VN:NS virus. In a guinea pig model, the rK09/VN:NS-PBM virus showed even greater transmission efficiency than the rK/09 virus. These results suggest that the PBM in the NS1 protein may determine viral persistence in the human and avian IAV interface.


Subject(s)
Influenza A Virus, H1N1 Subtype/physiology , Influenza, Human/transmission , Influenza, Human/virology , PDZ Domains , Viral Nonstructural Proteins/chemistry , Viral Nonstructural Proteins/metabolism , Animals , Birds , Female , Guinea Pigs , Humans , Mice , Mice, Inbred BALB C , Structure-Activity Relationship , Virus Activation/physiology , Virus Replication/physiology
18.
Arch Virol ; 159(10): 2559-65, 2014 Oct.
Article in English | MEDLINE | ID: mdl-24824345

ABSTRACT

The surface glycoprotein hemagglutinin (HA) of influenza virus initiates the infection process by binding to sialic acid receptors on upper respiratory cells in the host. In contrast to avian influenza viruses, which bind to sialic acids connected by an α2-3 linkage to the penultimate galactose, human influenza viruses prefer sialic acids with an α2-6 linkage. Recently, there have been multiple cases of severe human infections associated with an HA D222G mutant influenza virus. In this study, we have investigated the pathogenic effects of the HA D222G substitution in a 2009 pandemic H1N1 virus in mice. Compared with the A/Korea/01/2009 (K/09) virus, the HA D222G mutant showed reduced growth in cells and reduced binding avidity to human and turkey red blood cells. In a BALB/c mouse infection model, infection with the HA D222G mutant virus resulted in less body weight loss when compared to the parental K/09 virus. Altogether, our data suggest that the HA D222G substitution in the K/09 virus might be deleterious to viral fitness.


Subject(s)
Hemagglutinin Glycoproteins, Influenza Virus/genetics , Influenza A Virus, H1N1 Subtype/genetics , Orthomyxoviridae Infections/pathology , Virus Attachment , Amino Acid Substitution , Animals , Binding Sites/genetics , Body Weight , Cell Line , Disease Models, Animal , Dogs , Female , HEK293 Cells , Humans , Influenza A Virus, H1N1 Subtype/pathogenicity , Influenza, Human , Madin Darby Canine Kidney Cells , Mice , Mice, Inbred BALB C , Virus Replication/genetics
19.
PLoS One ; 9(2): e88782, 2014.
Article in English | MEDLINE | ID: mdl-24523938

ABSTRACT

Influenza A virus (IAV) can infect avian and mammalian species, including humans. The genome nature of IAVs may contribute to viral adaptation in different animal hosts, resulting in gene reassortment and the reproduction of variants with optimal fitness. As seen again in the 2009 swine-origin influenza A H1N1 pandemic, pigs are known to be susceptible to swine, avian, and human IAVs and can serve as a 'mixing vessel' for the generation of novel IAV variants. To this end, the emergence of swine influenza viruses must be kept under close surveillance. Herein, we report the isolation and phylogenetic study of a swine IAV, A/swine/Korea/PL01/2012 (swPL01, H3N2 subtype). After screening nasopharyngeal samples from pigs in the Gyeongsangnam-do region of Korea from December 2011 to May 2012, we isolated the swPL01 virus and sequenced its all of 8 genome segments (polymerase basic 2, PB2; polymerase basic 1, PB1; polymerase acidic, PA; hemagglutinin, HA; nucleocapsid protein, NP; neuraminidase, NA; matrix protein, M; and nonstructural protein, NS). The phylogenetic study, analyzed with reference strains registered in the National Center for Biotechnology Information (NCBI) database, indicated that the swPL01 virus was similar to the North American triple-reassortant swine strains and that the HA gene of the swPL01 virus was categorized into swine H3 cluster IV. The swPL01 virus had the M gene of the triple-reassortant swine H3N2 viruses, whereas that of other contemporary strains in Korea was transferred from the 2009 pandemic H1N1 virus. These data suggest the possibility that various swine H3N2 viruses may co-circulate in Korea, which underlines the importance of a sustained surveillance system against swine IAVs.


Subject(s)
Influenza A Virus, H3N2 Subtype/genetics , Orthomyxoviridae Infections/virology , Phylogeny , Algorithms , Animals , Cluster Analysis , Hemagglutinin Glycoproteins, Influenza Virus/genetics , Humans , Influenza, Human/virology , Reassortant Viruses/genetics , Republic of Korea , Swine , Swine Diseases/virology
20.
J Microbiol ; 51(5): 676-81, 2013 Oct.
Article in English | MEDLINE | ID: mdl-24173646

ABSTRACT

Herbal medicine has been used in the orient for thousands of years to treat large and small ailments, including microbial infections. Although there are treatments for influenza virus infection, there is no treatment for drug-resistant viruses. It is time that we explored and exploited the multi-component nature of herbal extracts as multi-drug combination therapies. Here, we present data on the anti-influenza virus effect of a medicinal mushroom, Phellinus igniarius. The P. igniarius water extract was effective against influenza A and B viruses, including 2009 pandemic H1N1, human H3N2, avian H9N2, and oseltamivir-resistant H1N1 viruses. Virological assays revealed that the extract may interfere with one or more early events in the influenza virus replication cycle, including viral attachment to the target cell. Therefore, our results provide new insights into the use of P. igniarius as an anti-influenza medicine.


Subject(s)
Antiviral Agents/isolation & purification , Basidiomycota/chemistry , Influenza A virus/drug effects , Influenza B virus/drug effects , Humans , Influenza A virus/physiology , Influenza B virus/physiology , Microbial Sensitivity Tests , Orthomyxoviridae , Virus Attachment/drug effects , Virus Replication/drug effects
SELECTION OF CITATIONS
SEARCH DETAIL
...