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Biochemical Society Transactions Nov 2021Despite being considered the simplest form of life, bacteria remain enigmatic, particularly in light of pathogenesis and evolving antimicrobial resistance. After three... (Review)
Review
Despite being considered the simplest form of life, bacteria remain enigmatic, particularly in light of pathogenesis and evolving antimicrobial resistance. After three decades of genomics, we remain some way from understanding these organisms, and a substantial proportion of genes remain functionally unknown. Methodological advances, principally mass spectrometry (MS), are paving the way for parallel analysis of the proteome, metabolome and lipidome. Each provides a global, complementary assay, in addition to genomics, and the ability to better comprehend how pathogens respond to changes in their internal (e.g. mutation) and external environments consistent with infection-like conditions. Such responses include accessing necessary nutrients for survival in a hostile environment where co-colonizing bacteria and normal flora are acclimated to the prevailing conditions. Multi-omics can be harnessed across temporal and spatial (sub-cellular) dimensions to understand adaptation at the molecular level. Gene deletion libraries, in conjunction with large-scale approaches and evolving bioinformatics integration, will greatly facilitate next-generation vaccines and antimicrobial interventions by highlighting novel targets and pathogen-specific pathways. MS is also central in phenotypic characterization of surface biomolecules such as lipid A, as well as aiding in the determination of protein interactions and complexes. There is increasing evidence that bacteria are capable of widespread post-translational modification, including phosphorylation, glycosylation and acetylation; with each contributing to virulence. This review focuses on the bacterial genotype to phenotype transition and surveys the recent literature showing how the genome can be validated at the proteome, metabolome and lipidome levels to provide an integrated view of organism response to host conditions.
Topics: Adaptation, Physiological; Bacteria; Genotype; Host-Pathogen Interactions; Lipidomics; Mass Spectrometry; Metabolome; Phenotype; Protein Processing, Post-Translational; Proteome; Virulence
PubMed: 34374408
DOI: 10.1042/BST20191088 -
Molecular Aspects of Medicine Oct 2021Host-pathogen interactions at the molecular level are the key to fungal pathogenesis. Fungal pathogens utilize several mechanisms such as adhesion, invasion, phenotype... (Review)
Review
Host-pathogen interactions at the molecular level are the key to fungal pathogenesis. Fungal pathogens utilize several mechanisms such as adhesion, invasion, phenotype switching and metabolic adaptations, to survive in the host environment and respond. Post-transcriptional and translational regulations have emerged as key regulatory mechanisms ensuring the virulence and survival of fungal pathogens. Through these regulations, fungal pathogens effectively alter their protein pool, respond to various stress, and undergo morphogenesis, leading to efficient and comprehensive changes in fungal physiology. The regulation of virulence through post-transcriptional and translational regulatory mechanisms is mediated through mRNA elements (cis factors) or effector molecules (trans factors). The untranslated regions upstream and downstream of the mRNA, as well as various RNA-binding proteins involved in translation initiation or circularization of the mRNA, play pivotal roles in the regulation of morphology and virulence by influencing protein synthesis, protein isoforms, and mRNA stability. Therefore, post-transcriptional and translational mechanisms regulating the morphology, virulence and drug-resistance processes in fungal pathogens can be the target for new therapeutics. With improved "omics" technologies, these regulatory mechanisms are increasingly coming to the forefront of basic biology and drug discovery. This review aims to discuss various modes of post-transcriptional and translation regulations, and how these mechanisms exert influence in the virulence and morphogenesis of fungal pathogens.
Topics: Adaptation, Physiological; Gene Expression Regulation, Fungal; Humans; Protein Biosynthesis; Protein Processing, Post-Translational; Virulence
PubMed: 34497025
DOI: 10.1016/j.mam.2021.101017 -
Journal of Molecular Biology Nov 2019Recent studies revealed an amazing phenotypic heterogeneity between genetically identical individual cells within populations of microbial pathogens. During the course... (Review)
Review
Recent studies revealed an amazing phenotypic heterogeneity between genetically identical individual cells within populations of microbial pathogens. During the course of an infection, subpopulations occur, which differ in certain virulence-relevant factors, stress adaptation functions or physiological and metabolic abilities. The mechanisms driving this heterogeneity are divergent reactions of the pathogens to differences in host tissue microenvironments. In addition, certain genetic regulatory circuits with positive feedback loops and stochastic differences in gene expression can generate endogenous fluctuations in regulatory components leading to bistable expression of virulence-associated functions. Here, we focus on the occurrence of phenotypic heterogeneity in populations of well-studied examples of pathogens, which enables cooperative, social behavior where a subpopulation of producers shares fitness- and/or virulence-relevant goods and traits with non-producers. We further highlight that this strategy allows preadaptation of a subgroup of cells to recurrent and thus predictable changes of the environment that they encounter during the different stages of the infection. The diversity within bacterial communities has a significant influence on the survival of the pathogens within their hosts and the progression of the disease.
Topics: Adaptation, Physiological; Bacteria; Bacterial Physiological Phenomena; Biological Variation, Population; Host-Pathogen Interactions; Microbiological Phenomena; Nitric Oxide; Oxidation-Reduction; Phenotype; Reactive Oxygen Species; Stress, Physiological; Type III Secretion Systems; Virulence; Virulence Factors
PubMed: 31260693
DOI: 10.1016/j.jmb.2019.06.024 -
Advances in Genetics 2016Entomopathogenic fungi have been developed as environmentally friendly alternatives to chemical insecticides in biocontrol programs for agricultural pests and vectors of... (Review)
Review
Entomopathogenic fungi have been developed as environmentally friendly alternatives to chemical insecticides in biocontrol programs for agricultural pests and vectors of disease. However, mycoinsecticides currently have a small market share due to low virulence and inconsistencies in their performance. Genetic engineering has made it possible to significantly improve the virulence of fungi and their tolerance to adverse conditions. Virulence enhancement has been achieved by engineering fungi to express insect proteins and insecticidal proteins/peptides from insect predators and other insect pathogens, or by overexpressing the pathogen's own genes. Importantly, protein engineering can be used to mix and match functional domains from diverse genes sourced from entomopathogenic fungi and other organisms, producing insecticidal proteins with novel characteristics. Fungal tolerance to abiotic stresses, especially UV radiation, has been greatly improved by introducing into entomopathogens a photoreactivation system from an archaean and pigment synthesis pathways from nonentomopathogenic fungi. Conversely, gene knockout strategies have produced strains with reduced ecological fitness as recipients for genetic engineering to improve virulence; the resulting strains are hypervirulent, but will not persist in the environment. Coupled with their natural insect specificity, safety concerns can also be mitigated by using safe effector proteins with selection marker genes removed after transformation. With the increasing public concern over the continued use of synthetic chemical insecticides and growing public acceptance of genetically modified organisms, new types of biological insecticides produced by genetic engineering offer a range of environmentally friendly options for cost-effective control of insect pests.
Topics: Animals; Biological Control Agents; Fungi; Genetic Engineering; Insect Proteins; Insect Vectors; Insecta; Promoter Regions, Genetic; Safety; Ultraviolet Rays; Virulence
PubMed: 27131325
DOI: 10.1016/bs.adgen.2015.11.001 -
Phytopathology Oct 2018Among necrotrophic fungi, Sclerotinia sclerotiorum is remarkable for its extremely broad host range and for its aggressive host tissue colonization. With full genome... (Review)
Review
Among necrotrophic fungi, Sclerotinia sclerotiorum is remarkable for its extremely broad host range and for its aggressive host tissue colonization. With full genome sequencing, transcriptomic analyses and the increasing pace of functional gene characterization, the factors underlying the basis of this broad host range necrotrophic pathogenesis are now being elucidated at a greater pace. Among these, genes have been characterized that are required for infection via compound appressoria in addition to genes associated with colonization that regulate oxalic acid (OA) production and OA catabolism. Moreover, virulence-related secretory proteins have been identified, among which are candidates for manipulating host activities apoplastically and cytoplasmically. Coupled with these mechanistic studies, cytological observations of the colonization process have blurred the heretofore clear-cut biotroph versus necrotroph boundary. In this review, we reexamine the cytology of S. sclerotiorum infection and put more recent molecular and genomic data into the context of this cytology. We propose a two-phase infection model in which the pathogen first evades, counteracts and subverts host basal defense reactions prior to killing and degrading host cells. Spatially, the pathogen may achieve this via the production of compatibility factors/effectors in compound appressoria, bulbous subcuticular hyphae, and primary invasive hyphae. By examining the nuances of this interaction, we hope to illuminate new classes of factors as targets to improve our understanding of broad host range necrotrophic pathogens and provide the basis for understanding corresponding host resistance.
Topics: Ascomycota; Host Specificity; Plant Diseases; Plants; Virulence
PubMed: 30048598
DOI: 10.1094/PHYTO-06-18-0197-RVW -
Fungal Biology May 2023The Botryosphaeriaceae family comprises numerous fungal pathogens capable of causing economically meaningful diseases in a wide range of crops. Many of its members can...
The Botryosphaeriaceae family comprises numerous fungal pathogens capable of causing economically meaningful diseases in a wide range of crops. Many of its members can live as endophytes and turn into aggressive pathogens following the onset of environmental stress events. Their ability to cause disease may rely on the production of a broad set of effectors, such as cell wall-degrading enzymes, secondary metabolites, and peptidases. Here, we conducted comparative analyses of 41 genomes representing six Botryosphaeriaceae genera to provide insights into the genetic features linked to pathogenicity and virulence. We show that these Botryosphaeriaceae genomes possess a large diversity of carbohydrate-active enzymes (CAZymes; 128 families) and peptidases (45 families). Botryosphaeria, Neofusicoccum, and Lasiodiplodia presented the highest number of genes encoding CAZymes involved in the degradation of the plant cell wall components. The genus Botryosphaeria also exhibited the highest abundance of secreted CAZymes and peptidases. Generally, the secondary metabolites gene cluster profile was consistent in the Botryosphaeriaceae family, except for Diplodia and Neoscytalidium. At the strain level, Neofusicoccum parvum NpBt67 stood out among all the Botryosphaeriaceae genomes, presenting a higher number of secretome constituents. In contrast, the Diplodia strains showed the lowest richness of the pathogenicity- and virulence-related genes, which may correlate with their low virulence reported in previous studies. Overall, these results contribute to a better understanding of the mechanisms underlying pathogenicity and virulence in remarkable Botryosphaeriaceae species. Our results also support that Botryosphaeriaceae species could be used as an interesting biotechnological tool for lignocellulose fractionation and bioeconomy.
Topics: Virulence; Ascomycota; Plant Diseases
PubMed: 37142361
DOI: 10.1016/j.funbio.2023.03.004 -
Environmental Microbiology May 2017Plant pathogenic bacteria attack numerous agricultural crops, causing devastating effects on plant productivity and yield. They survive in diverse environments, both in... (Review)
Review
Plant pathogenic bacteria attack numerous agricultural crops, causing devastating effects on plant productivity and yield. They survive in diverse environments, both in plants, as pathogens, and also outside their hosts as saprophytes. Hence, they are confronted with numerous changing environmental parameters. During infection, plant pathogens have to deal with stressful conditions, such as acidic, oxidative and osmotic stresses; anaerobiosis; plant defenses; and contact with antimicrobial compounds. These adverse conditions can reduce bacterial survival and compromise disease initiation and propagation. Successful bacterial plant pathogens must detect potential hosts and also coordinate their possibly conflicting programs for survival and virulence. Consequently, these bacteria have a strong and finely tuned capacity for sensing and responding to environmental and plant stimuli. This review summarizes our current knowledge of the signals and genetic circuits that affect survival and virulence factor expression in three important and well-studied plant pathogenic bacteria with wide host ranges and the capacity for long-term environmental survival. These are: Ralstonia solanacerarum, a vascular pathogen that causes wilt disease; Agrobacterium tumefaciens, a biotrophic tumorigenic pathogen responsible for crown gall disease and Dickeya, a brute force apoplastic pathogen responsible for soft-rot disease.
Topics: Agrobacterium tumefaciens; Crops, Agricultural; Environment; Host Specificity; Host-Pathogen Interactions; Pectobacterium; Plant Diseases; Ralstonia solanacearum; Stress, Physiological; Virulence; Virulence Factors
PubMed: 27878915
DOI: 10.1111/1462-2920.13611 -
Molecular Biology of the Cell Dec 2015One quarter of all deaths worldwide each year result from infectious diseases caused by microbial pathogens. Pathogens infect and cause disease by producing virulence...
One quarter of all deaths worldwide each year result from infectious diseases caused by microbial pathogens. Pathogens infect and cause disease by producing virulence factors that target host cell molecules. Studying how virulence factors target host cells has revealed fundamental principles of cell biology. These include important advances in our understanding of the cytoskeleton, organelles and membrane-trafficking intermediates, signal transduction pathways, cell cycle regulators, the organelle/protein recycling machinery, and cell-death pathways. Such studies have also revealed cellular pathways crucial for the immune response. Discoveries from basic research on the cell biology of pathogenesis are actively being translated into the development of host-targeted therapies to treat infectious diseases. Thus there are many reasons for cell biologists to incorporate the study of microbial pathogens into their research programs.
Topics: Animals; Bacteria; Cell Biology; Host-Pathogen Interactions; Humans; Infections; Mice; Parasites; Signal Transduction; Virulence; Viruses
PubMed: 26628749
DOI: 10.1091/mbc.E15-03-0144 -
New Biotechnology Sep 2016Fungal pathogens are causal agents of numerous human, animal, and plant diseases. They employ various infection modes to overcome host defense systems. Infection... (Review)
Review
Fungal pathogens are causal agents of numerous human, animal, and plant diseases. They employ various infection modes to overcome host defense systems. Infection mechanisms of different fungi have been subjected to many comprehensive studies. These investigations have been facilitated by the development of various '-omics' techniques, and proteomics has one of the leading roles in this regard. Fungal conidia and sclerotia could be considered the most important structures for pathogenesis as their germination is one of the first steps towards a host infection. They represent interesting objects for proteomic studies because of the presence of unique proteins with unexplored biotechnological potential required for pathogen viability, development and the subsequent host infection. Proteomic peculiarities of survival structures of different fungi, including those of biotechnological significance (e.g., Asperillus fumigatus, A. nidulans, Metarhizium anisopliae), in a dormant state, as well as changes in the protein production during early stages of fungal development are the subjects of the present review. We focused on biological aspects of proteomic studies of fungal survival structures rather than on an evaluation of proteomic approaches. For that reason, proteins that have been identified in this context are discussed from the point of view of their involvement in different biological processes and possible functions assigned to them. This is the first review paper summarizing recent advances in proteomics of fungal survival structures.
Topics: Animals; Biotechnology; Fungal Proteins; Fungi; Host-Pathogen Interactions; Humans; Mycelium; Proteome; Proteomics; Spores, Fungal; Virulence
PubMed: 26777984
DOI: 10.1016/j.nbt.2015.12.011 -
Microbiological Research Sep 2023Quorum sensing (QS) is a communication mechanism that controls bacterial communication and can influence the transcriptional expression of multiple genes through one or... (Review)
Review
Quorum sensing (QS) is a communication mechanism that controls bacterial communication and can influence the transcriptional expression of multiple genes through one or more signaling molecules, thereby coordinating the population response of multiple bacterial pathogens. Secretion systems (SS) play an equally important role in bacterial information exchange, relying on the secretory systems to secrete proteins that act as virulence factors to promote adhesion to host cells. Eight highly efficient SS have been described, all of which are involved in the secretion or transfer of virulence factors, and the effector proteins they secrete play a key role in the virulence and pathogenicity of bacteria. It has been shown that many bacterial SS are directly or indirectly regulated by QS and thus influence bacterial virulence and antibiotic resistance. This review describes the relationship between QS and SS of several common zoonotic pathogenic bacteria and outlines the molecular mechanisms of how QS systems regulate SS, to provide a theoretical basis for the study of bacterial pathogenicity and the development of novel antibacterial drugs.
Topics: Quorum Sensing; Bacteria; Anti-Bacterial Agents; Virulence; Virulence Factors; Bacterial Proteins; Gene Expression Regulation, Bacterial
PubMed: 37343493
DOI: 10.1016/j.micres.2023.127436