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Drug Design, Development and Therapy 2016Pathogens deploy an arsenal of virulence factors (VFs) to establish themselves within their infectious niche. The discovery of antimicrobial compounds and their... (Review)
Review
Pathogens deploy an arsenal of virulence factors (VFs) to establish themselves within their infectious niche. The discovery of antimicrobial compounds and their development into therapeutics has made a monumental impact on human and microbial populations. Although humans have used antimicrobials for medicinal and agricultural purposes, microorganism populations have developed and shared resistance mechanisms to persevere in the face of classical antimicrobials. However, a positive substitute is antivirulence therapy; antivirulence therapeutics prevent or interrupt an infection by counteracting a pathogen's VFs. Their application can reduce the use of broad-spectrum antimicrobials and dampen the frequency with which resistant strains emerge. Here, we summarize the contribution of VFs to various acute and chronic infections. In correspondence with this, we provide an overview of the research and development of antivirulence strategies.
Topics: Anti-Bacterial Agents; Anti-Infective Agents; Humans; Quorum Sensing; Virulence; Virulence Factors
PubMed: 27313446
DOI: 10.2147/DDDT.S98939 -
Trends in Microbiology May 2020Bacterial pathogens employ diverse fitness and virulence mechanisms to gain an advantage in competitive niches. These lifestyle-specific traits require integration into... (Review)
Review
Bacterial pathogens employ diverse fitness and virulence mechanisms to gain an advantage in competitive niches. These lifestyle-specific traits require integration into the regulatory network of the cell and are often controlled by pre-existing transcription factors. In this review, we highlight recent advances that have been made in characterizing this regulatory flexibility in prominent members of the Enterobacteriaceae. We focus on the direct global interactions between transcription factors and their target genes in pathogenic Escherichia coli and Salmonella revealed using chromatin immunoprecipitation coupled with next-generation sequencing. Furthermore, the implications and advantages of such regulatory adaptations in benefiting distinct pathogenic lifestyles are discussed.
Topics: Chromatin Immunoprecipitation; Escherichia coli; Escherichia coli Infections; Gene Expression Regulation, Bacterial; High-Throughput Nucleotide Sequencing; Salmonella; Salmonella Infections; Transcription Factors; Transcription, Genetic; Virulence
PubMed: 32298614
DOI: 10.1016/j.tim.2020.01.002 -
Progress in Molecular Biology and... 2016The pectinolytic Dickeya spp. are Gram-negative bacteria causing severe disease in a wide range of plant species. Although the Dickeya genus was initially restricted to... (Review)
Review
The pectinolytic Dickeya spp. are Gram-negative bacteria causing severe disease in a wide range of plant species. Although the Dickeya genus was initially restricted to tropical and subtropical areas, two Dickeya species (D. dianthicola and D. solani) emerged recently in potato cultures in Europe. Soft-rot, the visible symptoms, is caused by plant cell wall degrading enzymes, mainly pectate lyases (Pels) that cleave the pectin polymer. However, an efficient colonization of the host requires many additional elements including early factors (eg, flagella, lipopolysaccharide, and exopolysaccharide) that allow adhesion of the bacteria and intermediate factors involved in adaptation to new growth conditions encountered in the host (eg, oxidative stress, iron starvation, and toxic compounds). To facilitate this adaptation, Dickeya have developed complex regulatory networks ensuring appropriate expression of virulence genes. This review presents recent advances in our understanding of the signals and genetic circuits impacting the expression of virulence determinants. Special attention is paid to integrated control of virulence functions by variations in the superhelical density of chromosomal DNA, and the global and specific regulators, making the regulation of Dickeya virulence an especially attractive model for those interested in relationships between the chromosomal dynamics and gene regulatory networks.
Topics: Adaptation, Physiological; Enterobacteriaceae; Host-Pathogen Interactions; Models, Biological; Plants; Virulence
PubMed: 27571692
DOI: 10.1016/bs.pmbts.2016.05.005 -
Methods in Molecular Biology (Clifton,... 2020An essential property associated with leptospiral virulence is the pathogen's ability to translocate across host cells, enabling Leptospira to evade the host immune...
An essential property associated with leptospiral virulence is the pathogen's ability to translocate across host cells, enabling Leptospira to evade the host immune response, disseminate, and establish infection. Cell monolayer translocation assay allows for the quantification of Leptospira strain's competence to cross cell barriers while measuring the integrity of the polarized eukaryotic cell monolayer during this process.
Topics: Animals; Biological Assay; Cell Line; Cell Movement; Cell Polarity; Dogs; Eukaryotic Cells; Leptospira; Leptospirosis; Madin Darby Canine Kidney Cells; Virulence
PubMed: 32632868
DOI: 10.1007/978-1-0716-0459-5_15 -
[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 -
Tuberculosis (Edinburgh, Scotland) Sep 2016The culturing of mycobacteria is a standard procedure that is consistent world-wide, with little variation in the growth media constituents, particularly those found in... (Review)
Review
The culturing of mycobacteria is a standard procedure that is consistent world-wide, with little variation in the growth media constituents, particularly those found in liquid and solid media. Before the 1940s however, the aggregating nature of mycobacteria as well as the characteristic slow growth-rate saw mycobacterial research delay considerably. Dubos and colleagues addressed both these issues and observed that a very small volume of Tween detergent was sufficient to greatly improve the culturing of mycobacteria. Over the years however, evidence of the unfavourable effects of this detergent on a number of morphological, biochemical, pathogenic and host-interacting properties of mycobacteria surfaced. For the first time we bring together literature, past and present to comprehensively review the mycobacterial properties which are, and are not affected by the use of this detergent. We also address other detergents and methods which may circumvent the need to include Tween compounds in mycobacterial culture media.
Topics: Bacteriological Techniques; Cell Wall; Culture Media; Detergents; Host-Pathogen Interactions; Humans; Microbial Sensitivity Tests; Mycobacterium; Virulence
PubMed: 27553410
DOI: 10.1016/j.tube.2016.07.002 -
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 -
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