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Journal of Virology Jul 2023Porcine epidemic diarrhea virus is a swine pathogen that has been responsible for significant animal and economic losses worldwide in recent years. In this manuscript,...
Porcine epidemic diarrhea virus is a swine pathogen that has been responsible for significant animal and economic losses worldwide in recent years. In this manuscript, we report the generation of a reverse genetics system C(RGS) for the highly virulent US PEDV strain Minnesota (PEDV-MN; GenBank accession number KF468752), which was based on the assembly and cloning of synthetic DNA, using vaccinia virus as a cloning vector. Viral rescue was only possible following the substitution of 2 nucleotides within the 5'UTR and 2 additional nucleotides within the spike gene, based on the sequence of the cell culture-adapted strains. Besides displaying a highly pathogenic phenotype in newborn piglets, in comparison with the parental virus, the rescued recombinant PEDV-MN was used to confirm that the PEDV spike gene has an important role in PEDV virulence and that the impact of an intact PEDV ORF3 on viral pathogenicity is modest. Moreover, a chimeric virus with a TGEV spike gene in the PEDV backbone generated with RGS was able to replicate efficiently and could be readily transmitted between piglets. Although this chimeric virus did not cause severe disease upon the initial infection of piglets, there was evidence of increasing pathogenicity upon transmission to contact piglets. The RGS described in this study constitutes a powerful tool with which to study PEDV pathogenesis and can be used to generate vaccines against porcine enteric coronaviruses. PEDV is a swine pathogen that is responsible for significant animal and economic losses worldwide. Highly pathogenic variants can lead to a mortality rate of up to 100% in newborn piglets. The generation of a reverse genetics system for a highly virulent PEDV strain originating from the United States is an important step in phenotypically characterizing PEDV. The synthetic PEDV mirrored the authentic isolate and displayed a highly pathogenic phenotype in newborn piglets. With this system, it was possible to characterize potential viral virulence factors. Our data revealed that an accessory gene (ORF3) has a limited impact on pathogenicity. However, as it is also now known for many coronaviruses, the PEDV spike gene is one of the main determinants of pathogenicity. Finally, we show that the spike gene of another porcine coronavirus, namely, TGEV, can be accommodated in the PEDV genome background, suggesting that similar viruses can emerge in the field via recombination.
Topics: Animals; United States; Swine; Virulence; Porcine epidemic diarrhea virus; Spike Glycoprotein, Coronavirus; Swine Diseases; Reverse Genetics; Coronavirus Infections; Nucleotides; Diarrhea
PubMed: 37358450
DOI: 10.1128/jvi.01964-22 -
[Isolation, identification, and pathogenicity research of brown rot pathogens from Gastrodia elata].Zhongguo Zhong Yao Za Zhi = Zhongguo... May 2022Brown rot is a common disease in the cultivation and production of Gastrodia elata, but its pathogens have not been fully revealed. In this study, the pathogenic fungi...
Brown rot is a common disease in the cultivation and production of Gastrodia elata, but its pathogens have not been fully revealed. In this study, the pathogenic fungi were isolated and purified from tubers of 77 G. elata samples with brown rot. Pathogens were identified by the pathogenicity test and morphological and molecular identification. The pathogenicity of each pathogen and its inhibitory effects on Armillaria gallica were compared. The results showed that 119 strains of fungi were isolated from tubers of G. elata infected with brown rot. Among them, the frequency of separation of Ilyonectria fungi was as high as 42.01%. The pathogenicity test showed that the pathogenicity characteristics of six strains of fungi were consistent with the natural symptoms of brown rot in G. elata. The morphological and molecular identification results showed that the six strains belonged to I. cyclaminicola and I. robusta in the Nectriaceae family of Sordariomycetes class, respectively. Both types of fungi could produce pigments, conidia, and chlamycospore, and the growth rate of I. cyclaminicola was significantly higher than that of I. robusta. The comparison of pathogenicity showed that the spots formed by I. cyclaminicola inoculation were significantly larger than those of I. robusta inoculation, suggesting I. cyclaminicola was superior to I. robusta in pathogenicity. The results of confrontation culture showed that I. cyclaminicola and I. robusta could signi-ficantly inhibit the germination and cordage growth of A. gallica. A. gallica also inhibited the growth of pathogens, and I. cyclaminicola was less inhibited as compared with I. robusta. The results of this study revealed for the first time that I. cyclaminicola and I. robusta were the pathogens responsible for G. elata brown rot.
Topics: Fungi; Gastrodia; Plant Tubers; Spores, Fungal; Virulence
PubMed: 35531674
DOI: 10.19540/j.cnki.cjcmm.20220223.102 -
Current Genetics Feb 2021Phyto-pathogenic fungi can cause huge damage to crop production. During millions of years of coexistence, fungi have evolved diverse life-style to obtain nutrients from... (Review)
Review
Phyto-pathogenic fungi can cause huge damage to crop production. During millions of years of coexistence, fungi have evolved diverse life-style to obtain nutrients from the host and to colonize upon them. They deploy various proteinaceous as well as non-proteinaceous secreted molecules commonly referred as effectors to sabotage host machinery during the infection process. The effectors are important virulence determinants of pathogenic fungi and play important role in successful pathogenesis, predominantly by avoiding host-surveillance system. However, besides being important for pathogenesis, the fungal effectors end-up being recognized by the resistant cultivars of the host, which mount a strong immune response to ward-off pathogens. Various recent studies involving different pathosystem have revealed the virulence/avirulence functions of fungal effectors and their involvement in governing the outcome of host-pathogen interactions. However, the effectors and their cognate resistance gene in the host remain elusive for several economically important fungal pathogens. In this review, using examples from some of the biotrophic, hemi-biotrophic and necrotrophic pathogens, we elaborate the double-edged functions of fungal effectors. We emphasize that knowledge of effector functions can be helpful in effective management of fungal diseases in crop plants.
Topics: Fungi; Host-Pathogen Interactions; Plant Diseases; Plants; Virulence; Virulence Factors
PubMed: 33146780
DOI: 10.1007/s00294-020-01118-3 -
Bulletin of Mathematical Biology Jan 2020In this work we propose a variant of a classical SIR epidemiological model where pathogens are characterized by a (phenotypic) mutant trait x. Imposing that the trait x...
In this work we propose a variant of a classical SIR epidemiological model where pathogens are characterized by a (phenotypic) mutant trait x. Imposing that the trait x mutates according to a random walk process and that it directly influences the epidemiological components of the pathogen, we studied its evolutionary development by interpreting the tenet of maximizing the basic reproductive number of the pathogen as an optimal control problem. Pontryagin's maximum principle was used to identify the possible optimal evolutionary strategies of the pathogen. Qualitatively, three types of optimal evolutionary routes were identified and interpreted in the context of virulence evolution. Each optimal solution imposes a different tradeoff relation among the epidemiological parameters. The results predict (mostly) two kinds of infections: short-lasting mild infections and long-lasting acute infections.
Topics: Animals; Basic Reproduction Number; Biological Evolution; Epidemics; Epidemiologic Factors; Host Microbial Interactions; Host-Parasite Interactions; Host-Pathogen Interactions; Humans; Infections; Mathematical Concepts; Models, Biological; Mutation; Virulence
PubMed: 31970536
DOI: 10.1007/s11538-019-00688-9 -
Microbiology Spectrum Feb 2023Verticillium dahliae Kleb is a typical soilborne pathogen that can cause vascular wilt disease on more than 400 plants. Functional analysis of genes related to the...
Verticillium dahliae Kleb is a typical soilborne pathogen that can cause vascular wilt disease on more than 400 plants. Functional analysis of genes related to the growth and virulence is crucial to revealing the molecular mechanism of the pathogenicity of V. dahliae. Glycosidase hydrolases can hydrolyze the glycosidic bond, and some can cause host plant immune response to V. dahliae. Here, we reported a functional validation of VdGAL4 as an α-galactosidase that belongs to glycoside hydrolase family 27. VdGAL4 could cause plant cell death, and its signal peptide plays an important role in cellular immune response. VdGAL4-triggered cell death depends on BAK1 and SOBIR1 in Nicotiana benthamiana. In V. dahliae, the function of in mycelial growth, conidia, microsclerotium, and pathogenicity was studied by constructing deletion and complementation mutants. Results showed that the deletion of reduced the conidial yield and conidial germination rate of V. dahliae and changed the microscopic morphology of conidia; the mycelia were arranged more disorderly and were unable to produce microsclerotium. The deletion mutants exhibited reduced utilization of different carbon sources, such as raffinose and sucrose. The deletion mutants were also more sensitive to abiotic stress agents of SDS, sorbitol, low-temperature stress of 16°C, and high-temperature stress of 45°C. In addition, the deletion mutants lost the ability to penetrate cellophane and its mycelium were disorderly arranged. Remarkably, deletion mutants exhibited reduced pathogenicity of V. dahliae. These results showed that played a critical role in the pathogenicity of V. dahliae by regulating mycelial growth, conidial morphology, and the formation of microsclerotium. This study showed that α-galactosidase of V. dahliae could activate plant immune response and plays an important role in conidial morphology and yield, formation of microsclerotia, and mycelial penetration. deletion mutants significantly reduced the pathogenicity of V. dahliae. These findings deepened the understanding of pathogenic virulence factors and how the mechanism of pathogenic fungi infected the host, which may help to seek new strategies for effective control of plant diseases caused by pathogenic fungi.
Topics: Virulence; alpha-Galactosidase; Verticillium; Virulence Factors; Ascomycota; Plants; Plant Diseases; Fungal Proteins
PubMed: 36475739
DOI: 10.1128/spectrum.03515-22 -
Virulence Dec 2021is a saprophytic gram-positive bacterium, and an opportunistic foodborne pathogen that can produce listeriosis in humans and animals. It has evolved an exceptional...
is a saprophytic gram-positive bacterium, and an opportunistic foodborne pathogen that can produce listeriosis in humans and animals. It has evolved an exceptional ability to adapt to stress conditions encountered in different environments, resulting in a ubiquitous distribution. Because some food preservation methods and disinfection protocols in food-processing environments cannot efficiently prevent contaminations, constitutes a threat to human health and a challenge to food safety. In the host, colonizes the gastrointestinal tract, crosses the intestinal barrier, and disseminates through the blood to target organs. In immunocompromised individuals, the elderly, and pregnant women, the pathogen can cross the blood-brain and placental barriers, leading to neurolisteriosis and materno-fetal listeriosis. Molecular and cell biology studies of infection have proven to be a versatile pathogen that deploys unique strategies to invade different cell types, survive and move inside the eukaryotic host cell, and spread from cell to cell. Here, we present the multifaceted life cycle from a comprehensive perspective. We discuss genetic features of pathogenic species, analyze factors involved in food contamination, and review bacterial strategies to tolerate stresses encountered both during food processing and along the host's gastrointestinal tract. Then we dissect host-pathogen interactions underlying listerial pathogenesis in mammals from a cell biology and systemic point of view. Finally, we summarize the epidemiology, pathophysiology, and clinical features of listeriosis in humans and animals. This work aims to gather information from different fields crucial for a comprehensive understanding of the pathogenesis of
Topics: Adaptation, Physiological; Aged; Animals; Female; Humans; Listeria monocytogenes; Listeriosis; Mammals; Placenta; Pregnancy; Virulence
PubMed: 34612177
DOI: 10.1080/21505594.2021.1975526 -
Gene May 2024Pokkah Boeng disease (PBD), caused by Fusarium sacchari, severely affects sugarcane yield and quality. Necrosis-inducing secreted protein 1 (Nis1) is a fungal secreted...
Pokkah Boeng disease (PBD), caused by Fusarium sacchari, severely affects sugarcane yield and quality. Necrosis-inducing secreted protein 1 (Nis1) is a fungal secreted effector that induces necrotic lesions in plants. It interacts with host receptor-like kinases and inhibits their kinase activity. FsNis1 contains the Nis1 structure and triggered a pathogen-associated molecular pattern-triggered immune response in Nicotiana benthamiana, as reflected by causing reactive oxygen species production, callose accumulation, and the upregulated expression of defense response genes. Knockout of this gene in F. sacchari revealed a significant reduction in its pathogenicity, whereas the pathogenicity of the complementary mutant recovered to the wild-type levels, making this gene an important virulence factor for F. sacchari. In addition, the signal peptide of FsNis1 was required for the induction of cell death and PTI response in N. benthamiana. Thus, FsNis1 may not only be a key virulence factor for F. sacchari but may also induce defense responses in plants. These findings provide new insights into the function of Nis1 in host-pathogen interactions.
Topics: Fusarium; Plant Immunity; Virulence; Virulence Factors; Plant Diseases
PubMed: 38342252
DOI: 10.1016/j.gene.2024.148260 -
Genes Jul 2021RNA modifications are involved in numerous biological processes and are present in all RNA classes. These modifications can be constitutive or modulated in response to... (Review)
Review
RNA modifications are involved in numerous biological processes and are present in all RNA classes. These modifications can be constitutive or modulated in response to adaptive processes. RNA modifications play multiple functions since they can impact RNA base-pairings, recognition by proteins, decoding, as well as RNA structure and stability. However, their roles in stress, environmental adaptation and during infections caused by pathogenic bacteria have just started to be appreciated. With the development of modern technologies in mass spectrometry and deep sequencing, recent examples of modifications regulating host-pathogen interactions have been demonstrated. They show how RNA modifications can regulate immune responses, antibiotic resistance, expression of virulence genes, and bacterial persistence. Here, we illustrate some of these findings, and highlight the strategies used to characterize RNA modifications, and their potential for new therapeutic applications.
Topics: Bacteria; Host Adaptation; Host-Pathogen Interactions; RNA Processing, Post-Transcriptional; RNA, Bacterial; Virulence
PubMed: 34440299
DOI: 10.3390/genes12081125 -
Nature Communications Jan 2023Host bottlenecks prevent many infections before the onset of disease by eliminating invading pathogens. By monitoring the diversity of a barcoded population of the...
Host bottlenecks prevent many infections before the onset of disease by eliminating invading pathogens. By monitoring the diversity of a barcoded population of the diarrhea causing bacterium Citrobacter rodentium during colonization of its natural host, mice, we determine the number of cells that found the infection by establishing a replicative niche. In female mice the size of the pathogen's founding population scales with dose and is controlled by a severe yet slow-acting bottleneck. Reducing stomach acid or changing host genotype modestly relaxes the bottleneck without breaking the fractional relationship between dose and founders. In contrast, disrupting the microbiota causes the founding population to no longer scale with the size of the inoculum and allows the pathogen to infect at almost any dose, indicating that the microbiota creates the dominant bottleneck. Further, in the absence of competition with the microbiota, the diversity of the pathogen population slowly contracts as the population is overtaken by bacteria having lost the critical virulence island, the locus of enterocyte effacement (LEE). Collectively, our findings reveal that the mechanisms of protection by colonization bottlenecks are reflected in and can be generally defined by the impact of dose on the pathogen's founding population.
Topics: Female; Animals; Mice; Virulence; Bacteria; Virulence Factors; Enterocytes; Diarrhea; Citrobacter rodentium; Enterobacteriaceae Infections
PubMed: 36709326
DOI: 10.1038/s41467-023-36162-3 -
Clinical Microbiology and Infection :... Jun 2024Mycobacterium abscessus belongs to the largest group of mycobacteria, the rapid-growing saprophytic mycobacteria, and is one of the most difficult-to-treat opportunistic... (Review)
Review
BACKGROUND
Mycobacterium abscessus belongs to the largest group of mycobacteria, the rapid-growing saprophytic mycobacteria, and is one of the most difficult-to-treat opportunistic pathogen. Several features pertain to the high adaptability of M. abscessus to the host. These include the capacity to survive and persist within amoebae, to transition from a smooth to a rough morphotype that occurs during the course of the disease and to express of a wide array of virulence factors.
OBJECTIVES
The main objective of this narrative review consists to report major assets of M. abscessus that contribute to the virulence of these rapid-growing saprophytic mycobacteria. Strikingly, many of these determinants, whether they are from a mycobacterial origin or acquired by horizontal gene transfer, are known virulence factors found in slow-growing and strict pathogens for humans and animals.
SOURCES
In the light of recent published work in the field we attempted to highlight major features characterizing M. abscessus pathogenicity and to explain why this led to the emergence of this mycobacterial species in patients with cystic fibrosis.
CONTENT
M. abscessus genome plasticity, the smooth-to-rough transition, and the expression of a panel of enzymes associated with virulence in other bacteria are key players in M. abscessus virulence. In addition, the very large repertoire of lipid transporters, known as mycobacterial membrane protein large and small (MmpL and MmpS respectively), deeply influences the pathogenicity of M. abscessus, as exemplified here for some of them.
IMPLICATIONS
All these traits largely contribute to make M. abscessus a unique mycobacterium regarding to its pathophysiological processes, ranging from the early colonization steps to the establishment of severe and chronic pulmonary diseases.
Topics: Mycobacterium abscessus; Humans; Virulence Factors; Virulence; Mycobacterium Infections, Nontuberculous; Animals; Genome, Bacterial; Cystic Fibrosis
PubMed: 37797823
DOI: 10.1016/j.cmi.2023.08.036