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Nature Microbiology Jan 2020Microbial pathogens possess an arsenal of strategies to invade their hosts, evade immune defences and promote infection. In particular, bacteria use virulence factors,... (Review)
Review
Microbial pathogens possess an arsenal of strategies to invade their hosts, evade immune defences and promote infection. In particular, bacteria use virulence factors, such as secreted toxins and effector proteins, to manipulate host cellular processes and establish a replicative niche. Survival of eukaryotic organisms in the face of such challenge requires host mechanisms to detect and counteract these pathogen-specific virulence strategies. In this Review, we focus on effector-triggered immunity (ETI) in metazoan organisms as a mechanism for pathogen sensing and distinguishing pathogenic from non-pathogenic microorganisms. For the purposes of this Review, we adopt the concept of ETI formulated originally in the context of plant pathogens and their hosts, wherein specific host proteins 'guard' central cellular processes and trigger inflammatory responses following pathogen-driven disruption of these processes. While molecular mechanisms of ETI are well-described in plants, our understanding of functionally analogous mechanisms in metazoans is still emerging. In this Review, we present an overview of ETI in metazoans and discuss recently described cellular processes that are guarded by the host. Although all pathogens manipulate host pathways, we focus primarily on bacterial pathogens and highlight pathways of effector-triggered immune defence that sense disruption of core cellular processes by pathogens. Finally, we discuss recent developments in our understanding of how pathogens can evade ETI to overcome these host adaptations.
Topics: Animals; Bacteria; Bacterial Infections; Immune Evasion; Immunity, Innate; Inflammasomes; Receptors, Pattern Recognition; Signal Transduction; Virulence; Virulence Factors
PubMed: 31857733
DOI: 10.1038/s41564-019-0623-2 -
Microbiology Spectrum Oct 2014Gram-positive bacteria are leading causes of many types of human infection, including pneumonia, skin and nasopharyngeal infections, as well as urinary tract and... (Review)
Review
Gram-positive bacteria are leading causes of many types of human infection, including pneumonia, skin and nasopharyngeal infections, as well as urinary tract and surgical wound infections among hospitalized patients. These infections have become particularly problematic because many of the species causing them have become highly resistant to antibiotics. The role of mobile genetic elements, such as plasmids, in the dissemination of antibiotic resistance among Gram-positive bacteria has been well studied; less well understood is the role of mobile elements in the evolution and spread of virulence traits among these pathogens. While these organisms are leading agents of infection, they are also prominent members of the human commensal ecology. It appears that these bacteria are able to take advantage of the intimate association between host and commensal, via virulence traits that exacerbate infection and cause disease. However, evolution into an obligate pathogen has not occurred, presumably because it would lead to rejection of pathogenic organisms from the host ecology. Instead, in organisms that exist as both commensal and pathogen, selection has favored the development of mechanisms for variability. As a result, many virulence traits are localized on mobile genetic elements, such as virulence plasmids and pathogenicity islands. Virulence traits may occur within a minority of isolates of a given species, but these minority populations have nonetheless emerged as a leading problem in infectious disease. This chapter reviews virulence plasmids in nonsporulating Gram-positive bacteria, and examines their contribution to disease pathogenesis.
Topics: Animals; Bacterial Infections; Gene Transfer, Horizontal; Gram-Positive Bacteria; Humans; Plasmids; Virulence; Virulence Factors
PubMed: 25544937
DOI: 10.1128/microbiolspec.PLAS-0002-2013 -
Fungal Genetics and Biology : FG & B Sep 2017Fungi, like other organisms, actively sense the environmental light conditions in order to drive adaptive responses, including protective mechanisms against the... (Review)
Review
Fungi, like other organisms, actively sense the environmental light conditions in order to drive adaptive responses, including protective mechanisms against the light-associated stresses, and to regulate development. Ecological niches are characterized by different light regimes, for instance light is absent underground, and light spectra from the sunlight are changed underwater or under the canopy of foliage due to the absorption of distinct wavelengths by bacterial, algal and plant pigments. Considering the fact that fungi have evolved to adapt to their habitats, the complexities of their 'visual' systems may vary significantly. Fungi that are pathogenic on plants experience a special light regime because the host always seeks the optimum light conditions for photosynthesis - and the pathogen has to cope with this environment. When the pathogen lives under the canopy and is indirectly exposed to sunlight, it is confronted with an altered light spectrum enriched for green and far-red light. Botrytis cinerea, the gray mold fungus, is an aggressive plant pathogen mainly infecting the above-ground parts of the plant. As outlined in this review, the Leotiomycete maintains a highly sophisticated light signaling machinery, integrating (near)-UV, blue, green, red and far-red light signals by use of at least eleven potential photoreceptors to trigger a variety of responses, i.e. protection (pigmentation, enzymatic systems), morphogenesis (conidiation, apothecial development), entrainment of a circadian clock, and positive and negative tropism of multicellular (conidiophores, apothecia) and unicellular structures (conidial germ tubes). In that sense, 'looking through the eyes' of this plant pathogen will expand our knowledge of fungal photobiology.
Topics: Botrytis; Circadian Clocks; Cryptochromes; Light; Photoreceptors, Microbial; Phototropism; Plant Components, Aerial; Signal Transduction; Virulence
PubMed: 28648816
DOI: 10.1016/j.fgb.2017.06.002 -
Molecular Plant Pathology Oct 2016Most classical plant hormones are also produced by pathogenic and symbiotic fungi. The way in which these molecules favour the invasion of plant tissues and the... (Review)
Review
Most classical plant hormones are also produced by pathogenic and symbiotic fungi. The way in which these molecules favour the invasion of plant tissues and the development of fungi inside plant tissues is still largely unknown. In this review, we examine the different roles of such hormone production by pathogenic fungi. Converging evidence suggests that these fungal-derived molecules have potentially two modes of action: (i) they may perturb plant processes, either positively or negatively, to favour invasion and nutrient uptake; and (ii) they may also act as signals for the fungi themselves to engage appropriate developmental and physiological processes adapted to their environment. Indirect evidence suggests that abscisic acid, gibberellic acid and ethylene produced by fungi participate in pathogenicity. There is now evidence that auxin and cytokinins could be positive regulators required for virulence. Further research should establish whether or not fungal-derived hormones act like other fungal effectors.
Topics: Fungi; Host-Pathogen Interactions; Plant Growth Regulators; Plants; Virulence; Virulence Factors
PubMed: 26950404
DOI: 10.1111/mpp.12393 -
F1000Research 2019Morphological changes are critical for the virulence of a range of plant and human fungal pathogens. is a major human fungal pathogen whose ability to switch between... (Review)
Review
Morphological changes are critical for the virulence of a range of plant and human fungal pathogens. is a major human fungal pathogen whose ability to switch between different morphological states is associated with its adaptability and pathogenicity. In particular, can switch from an oval yeast form to a filamentous hyphal form, which is characteristic of filamentous fungi. What mechanisms underlie hyphal growth and how are they affected by environmental stimuli from the host or resident microbiota? These questions are the focus of intensive research, as understanding hyphal growth has broad implications for cell biological and medical research.
Topics: Candida albicans; Humans; Hyphae; Virulence
PubMed: 31131089
DOI: 10.12688/f1000research.18546.1 -
Journal of Plant Physiology Jan 2021Attempted infections of plants with fungi result in diverse outcomes ranging from symptom-less resistance to severe disease and even death of infected plants. The... (Review)
Review
Attempted infections of plants with fungi result in diverse outcomes ranging from symptom-less resistance to severe disease and even death of infected plants. The deleterious effect on crop yield have led to intense focus on the cellular and molecular mechanisms that explain the difference between resistance and susceptibility. This research has uncovered plant resistance or susceptibility genes that explain either dominant or recessive inheritance of plant resistance with many of them coding for receptors that recognize pathogen invasion. Approaches based on cell biology and phytochemistry have contributed to identifying factors that halt an invading fungal pathogen from further invasion into or between plant cells. Plant chemical defence compounds, antifungal proteins and structural reinforcement of cell walls appear to slow down fungal growth or even prevent fungal penetration in resistant plants. Additionally, the hypersensitive response, in which a few cells undergo a strong local immune reaction, including programmed cell death at the site of infection, stops in particular biotrophic fungi from spreading into surrounding tissue. In this review, we give a general overview of plant recognition and defence of fungal parasites tracing back to the early 20th century with a special focus on Triticeae and on the progress that was made in the last 30 years.
Topics: Disease Resistance; Fungi; Gene Expression Regulation, Fungal; Gene Expression Regulation, Plant; Genes, Plant; Host-Pathogen Interactions; Plant Diseases; Poaceae; Virulence
PubMed: 33249386
DOI: 10.1016/j.jplph.2020.153324 -
Frontiers in Immunology 2019Brucellosis is one of the most prevalent bacterial zoonosis of worldwide distribution. The disease is caused by spp., facultative intracellular pathogens. Brucellosis... (Review)
Review
Brucellosis is one of the most prevalent bacterial zoonosis of worldwide distribution. The disease is caused by spp., facultative intracellular pathogens. Brucellosis in animals results in abortion of fetuses, while in humans, it frequently manifests flu-like symptoms and a typical undulant fever, being osteoarthritis a common complication of the chronic infection. The two most common ways to acquire the infection in humans are through the ingestion of contaminated dairy products or by inhalation of contaminated aerosols. spp. enter the body mainly through the gastrointestinal and respiratory mucosa; however, most studies of immune response to spp. are performed analyzing models of systemic immunity. It is necessary to better understand the mucosal immune response induced by infection since this is the main entry site for the bacterium. In this review, some virulence factors and the mechanisms needed for pathogen invasion and persistence are discussed. Furthermore, some aspects of local immune responses induced during infection will be reviewed. With this knowledge, better vaccines can be designed focused on inducing protective mucosal immune response.
Topics: Brucella; Brucellosis; Humans; Immunity, Mucosal; Intestinal Mucosa; Respiratory Mucosa; Virulence
PubMed: 31481953
DOI: 10.3389/fimmu.2019.01759 -
Journal of Invertebrate Pathology Sep 2019The development of infectious diseases represents an outcome of dynamic interactions between the disease-producing agent's pathogenicity and the host's self-defense... (Review)
Review
The development of infectious diseases represents an outcome of dynamic interactions between the disease-producing agent's pathogenicity and the host's self-defense mechanism. Proteases secreted by pathogenic microorganisms and protease inhibitors produced by host species play an important role in the process. This review aimed at summarizing major findings in research on pathogen proteases and host protease inhibitors that had been proposed to be related to the development of mollusk diseases. Metalloproteases and serine proteases respectively belonging to Family M4 and Family S8 of the MEROPS system are among the most studied proteases that may function as virulence factors in mollusk pathogens. On the other hand, a mollusk-specific family (Family I84) of novel serine protease inhibitors and homologues of the tissue inhibitor of metalloprotease have been studied for their potential in the molluscan host defense. In addition, research at the genomic and transcriptomic levels showed that more proteases of pathogens and protease inhibitor of hosts are likely involved in mollusk disease processes. Therefore, the pathological significance of interactions between pathogen proteases and host protease inhibitors in the development of molluscan infectious diseases deserves more research efforts.
Topics: Animals; Host-Pathogen Interactions; Mollusca; Peptide Hydrolases; Virulence; Virulence Factors
PubMed: 31348922
DOI: 10.1016/j.jip.2019.107214 -
Molecular Plant Pathology Jul 2021Plant-pathogenic fungi are a significant threat to economic and food security worldwide. Novel protection strategies are required and therefore it is critical we... (Review)
Review
Plant-pathogenic fungi are a significant threat to economic and food security worldwide. Novel protection strategies are required and therefore it is critical we understand the mechanisms by which these pathogens cause disease. Virulence factors and pathogenicity genes have been identified, but in many cases their roles remain elusive. It is becoming increasingly clear that gene regulation is vital to enable plant infection and transcription factors play an essential role. Efforts to determine their regulatory functions in plant-pathogenic fungi have expanded since the annotation of fungal genomes revealed the ubiquity of transcription factors from a broad range of families. This review establishes the significance of transcription factors as regulatory elements in plant-pathogenic fungi and provides a systematic overview of those that have been functionally characterized. Detailed analysis is provided on regulators from well-characterized families controlling various aspects of fungal metabolism, development, stress tolerance, and the production of virulence factors such as effectors and secondary metabolites. This covers conserved transcription factors with either specialized or nonspecialized roles, as well as recently identified regulators targeting key virulence pathways. Fundamental knowledge of transcription factor regulation in plant-pathogenic fungi provides avenues to identify novel virulence factors and improve our understanding of the regulatory networks linked to pathogen evolution, while transcription factors can themselves be specifically targeted for disease control. Areas requiring further insight regarding the molecular mechanisms and/or specific classes of transcription factors are identified, and direction for future investigation is presented.
Topics: Fungal Proteins; Fungi; Gene Expression Regulation, Fungal; Genome, Fungal; Plant Diseases; Plants; Transcription Factors; Virulence; Virulence Factors
PubMed: 33973705
DOI: 10.1111/mpp.13056 -
Trends in Microbiology Jul 2022One billion people worldwide are affected by fungal pathogens, of which 1.6 million succumb to fungal infections per year. This review discusses the emergence and... (Review)
Review
One billion people worldwide are affected by fungal pathogens, of which 1.6 million succumb to fungal infections per year. This review discusses the emergence and evolution of fungal pathogenesis in humans in the form of opportunistic commensal and environmental fungi. We explore the attributes that contribute to their success as pathogens and the scenarios which may have caused the evolutionary selection of virulence factors. This includes antivirulence and avirulence genes, notions that are new for fungal pathogens of humans but which are based on well established concepts in bacterial pathogens and phytopathogenic fungi. These ideas will ultimately help us to better understand the pathogenicity of fungi that infect humans: from the emergence to the finer adjustment of virulence to promote pathogen persistence.
Topics: Fungi; Humans; Mycoses; Virulence; Virulence Factors
PubMed: 35058122
DOI: 10.1016/j.tim.2021.12.013