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1.
Annu Rev Immunol ; 40: 121-141, 2022 04 26.
Artículo en Inglés | MEDLINE | ID: mdl-35007128

RESUMEN

Invasive fungal diseases are rare in individuals with intact immunity. This, together with the fact that there are only a few species that account for most mycotic diseases, implies a remarkable natural resistance to pathogenic fungi. Mammalian immunity to fungi rests on two pillars, powerful immune mechanisms and elevated temperatures that create a thermal restriction zone for most fungal species. Conditions associated with increased susceptibility generally reflect major disturbances of immune function involving both the cellular and humoral innate and adaptive arms, which implies considerable redundancy in host defense mechanisms against fungi. In general, tissue fungal invasion is controlled through either neutrophil or granulomatous inflammation, depending on the fungal species. Neutrophils are critical against Candida spp. and Aspergillus spp. while macrophages are essential for controlling mycoses due to Cryptococcus spp., Histoplasma spp., and other fungi. The increasing number of immunocompromised patients together with climate change could significantly increase the prevalence of fungal diseases.


Asunto(s)
Micosis , Animales , Hongos , Humanos , Inmunidad Innata , Huésped Inmunocomprometido , Macrófagos , Mamíferos
2.
Annu Rev Immunol ; 36: 157-191, 2018 04 26.
Artículo en Inglés | MEDLINE | ID: mdl-29237128

RESUMEN

In the last few decades, the AIDS pandemic and the significant advances in the medical management of individuals with neoplastic and inflammatory conditions have resulted in a dramatic increase in the population of immunosuppressed patients with opportunistic, life-threatening fungal infections. The parallel development of clinically relevant mouse models of fungal disease and the discovery and characterization of several inborn errors of immune-related genes that underlie inherited human susceptibility to opportunistic mycoses have significantly expanded our understanding of the innate and adaptive immune mechanisms that protect against ubiquitous fungal exposures. This review synthesizes immunological knowledge derived from basic mouse studies and from human cohorts and provides an overview of mammalian antifungal host defenses that show promise for informing therapeutic and vaccination strategies for vulnerable patients.


Asunto(s)
Interacciones Huésped-Patógeno/inmunología , Micosis/inmunología , Micosis/microbiología , Síndrome de Inmunodeficiencia Adquirida/complicaciones , Síndrome de Inmunodeficiencia Adquirida/inmunología , Inmunidad Adaptativa , Animales , Susceptibilidad a Enfermedades , Vacunas Fúngicas/inmunología , Hongos/inmunología , Humanos , Sistema Inmunológico/citología , Sistema Inmunológico/inmunología , Sistema Inmunológico/metabolismo , Inmunidad Innata , Huésped Inmunocomprometido , Inmunoterapia , Micosis/prevención & control , Micosis/terapia , Transducción de Señal
3.
Cell ; 187(19): 5121-5127, 2024 Sep 19.
Artículo en Inglés | MEDLINE | ID: mdl-39303681

RESUMEN

Fungi play critical roles in the homeostasis of ecosystems globally and have emerged as significant causes of an expanding repertoire of devastating diseases in plants, animals, and humans. In this Commentary, we highlight the importance of fungal pathogens and argue for concerted research efforts to enhance understanding of fungal virulence, antifungal immunity, novel drug targets, antifungal resistance, and the mycobiota to improve human health.


Asunto(s)
Hongos , Micosis , Hongos/patogenicidad , Humanos , Micosis/microbiología , Micosis/inmunología , Animales , Farmacorresistencia Fúngica , Antifúngicos/farmacología , Virulencia
4.
Annu Rev Immunol ; 34: 317-34, 2016 05 20.
Artículo en Inglés | MEDLINE | ID: mdl-27168241

RESUMEN

CD4(+) T helper (Th) cells play a central role in the adaptive immune response by providing help to B cells and cytotoxic T cells and by releasing different types of cytokines in tissues to mediate protection against a wide range of pathogenic microorganisms. These functions are performed by different types of Th cells endowed with distinct migratory capacities and effector functions. Here we discuss how studies of the human T cell response to microbes have advanced our understanding of Th cell functional heterogeneity, in particular with the discovery of a distinct Th1 subset involved in the response to Mycobacteria and the characterization of two types of Th17 cells specific for extracellular bacteria or fungi. We also review new approaches to dissect at the clonal level the human CD4(+) T cell response induced by pathogens or vaccines that have revealed an unexpected degree of intraclonal diversification and propose a progressive and selective model of CD4(+) T cell differentiation.


Asunto(s)
Inmunidad Adaptativa , Infecciones Bacterianas/inmunología , Biodiversidad , Micosis/inmunología , Células TH1/inmunología , Células Th17/inmunología , Vacunas/inmunología , Animales , Antígenos CD4/metabolismo , Diferenciación Celular , Selección Clonal Mediada por Antígenos , Células Clonales , Citotoxicidad Inmunológica , Humanos , Inmunidad Humoral , Receptores de Antígenos de Linfocitos T/genética , Receptores de Antígenos de Linfocitos T/metabolismo
5.
Nat Immunol ; 23(12): 1735-1748, 2022 12.
Artículo en Inglés | MEDLINE | ID: mdl-36456734

RESUMEN

The non-pathogenic TH17 subset of helper T cells clears fungal infections, whereas pathogenic TH17 cells cause inflammation and tissue damage; however, the mechanisms controlling these distinct responses remain unclear. Here we found that fungi sensing by the C-type lectin dectin-1 in human dendritic cells (DCs) directed the polarization of non-pathogenic TH17 cells. Dectin-1 signaling triggered transient and intermediate expression of interferon (IFN)-ß in DCs, which was mediated by the opposed activities of transcription factors IRF1 and IRF5. IFN-ß-induced signaling led to integrin αvß8 expression directly and to the release of the active form of the cytokine transforming growth factor (TGF)-ß indirectly. Uncontrolled IFN-ß responses as a result of IRF1 deficiency induced high expression of the IFN-stimulated gene BST2 in DCs and restrained TGF-ß activation. Active TGF-ß was required for polarization of non-pathogenic TH17 cells, whereas pathogenic TH17 cells developed in the absence of active TGF-ß. Thus, dectin-1-mediated modulation of type I IFN responses allowed TGF-ß activation and non-pathogenic TH17 cell development during fungal infections in humans.


Asunto(s)
Células Dendríticas , Interferón Tipo I , Micosis , Humanos , Citocinas/metabolismo , Células Dendríticas/metabolismo , Interferón Tipo I/metabolismo , Lectinas Tipo C/genética , Lectinas Tipo C/metabolismo , Células Th17/metabolismo , Factor de Crecimiento Transformador beta/metabolismo , Micosis/inmunología
6.
Annu Rev Immunol ; 30: 115-48, 2012.
Artículo en Inglés | MEDLINE | ID: mdl-22224780

RESUMEN

Only a handful of the more than 100,000 fungal species on our planet cause disease in humans, yet the number of life-threatening fungal infections in patients has recently skyrocketed as a result of advances in medical care that often suppress immunity intensely. This emerging crisis has created pressing needs to clarify immune defense mechanisms against fungi, with the ultimate goal of therapeutic applications. Herein, we describe recent insights in understanding the mammalian immune defenses deployed against pathogenic fungi. The review focuses on adaptive immune responses to the major medically important fungi and emphasizes how dendritic cells and subsets in various anatomic compartments respond to fungi, recognize their molecular patterns, and signal responses that nurture and shape the differentiation of T cell subsets and B cells. Also emphasized is how the latter deploy effector and regulatory mechanisms that eliminate these nasty invaders while also constraining collateral damage to vital tissue.


Asunto(s)
Inmunidad Adaptativa , Hongos/inmunología , Micosis/inmunología , Animales , Diferenciación Celular/inmunología , Quimiocinas/inmunología , Citocinas/inmunología , Células Dendríticas/inmunología , Humanos , Inmunidad Innata , Inmunoglobulinas/inmunología , Receptores de Reconocimiento de Patrones/inmunología , Receptores de Reconocimiento de Patrones/metabolismo , Transducción de Señal , Linfocitos T/citología , Linfocitos T/inmunología , Linfocitos T/metabolismo
7.
Annu Rev Immunol ; 29: 1-21, 2011.
Artículo en Inglés | MEDLINE | ID: mdl-20936972

RESUMEN

Fungal diseases have emerged as significant causes of morbidity and mortality, particularly in immune-compromised individuals, prompting greater interest in understanding the mechanisms of host resistance to these pathogens. Consequently, the past few decades have seen a tremendous increase in our knowledge of the innate and adaptive components underlying the protective (and nonprotective) mechanisms of antifungal immunity. What has emerged from these studies is that phagocytic cells are essential for protection and that defects in these cells compromise the host's ability to resist fungal infection. This review covers the functions of phagocytes in innate antifungal immunity, along with selected examples of the strategies that are used by fungal pathogens to subvert these defenses.


Asunto(s)
Hongos , Micosis/inmunología , Fagocitos/inmunología , Inmunidad Adaptativa , Animales , Humanos , Evasión Inmune , Inmunidad Innata , Fagocitos/citología
8.
Nat Immunol ; 19(9): 912-922, 2018 09.
Artículo en Inglés | MEDLINE | ID: mdl-30131615

RESUMEN

Receptor-interacting protein (RIP) kinases, in particular RIPK1, RIPK2 and RIPK3, have emerged as pleiotropic modulators of inflammatory responses that act either by directly regulating intracellular inflammatory signaling pathways or by causing apoptotic or necrotic cell death. In this Review, we discuss the signaling pathways and immunological functions of these RIP kinases in the inflammatory response to microbial infection and tissue injury, as well as their potential roles in the pathogenesis of inflammatory disease and aging.


Asunto(s)
Envejecimiento/fisiología , Infecciones Bacterianas/inmunología , Inmunidad/inmunología , Inflamación/inmunología , Micosis/inmunología , Proteína Serina-Treonina Quinasas de Interacción con Receptores/inmunología , Animales , Muerte Celular , Humanos , Transducción de Señal
9.
Immunity ; 54(5): 856-858, 2021 05 11.
Artículo en Inglés | MEDLINE | ID: mdl-33979584

RESUMEN

Intestinal microbiome perturbation characterizes Crohn's disease (CD), though specific contributors to pathophysiology remain elusive. In a recent issue of Science, Jain et al. show that Debaryomyces hansenii impairs intestinal healing in mice via effects on type I interferon signaling and chemokine CCL5 expression in macrophages and that it is also prevalent in the inflamed mucosa of CD patients.


Asunto(s)
Enfermedad de Crohn/inmunología , Enfermedad de Crohn/microbiología , Mucosa Intestinal/microbiología , Cicatrización de Heridas/inmunología , Animales , Quimiocina CCL5/inmunología , Microbioma Gastrointestinal/inmunología , Humanos , Interferón Tipo I/inmunología , Mucosa Intestinal/inmunología , Macrófagos/inmunología , Ratones , Micosis/inmunología , Micosis/microbiología , Saccharomycetales/inmunología , Transducción de Señal/inmunología
10.
Nat Rev Mol Cell Biol ; 19(4): 262-274, 2018 04.
Artículo en Inglés | MEDLINE | ID: mdl-29209056

RESUMEN

Alterations in the regulation of gene expression are frequently associated with developmental diseases or cancer. Transcription activation is a key phenomenon in the regulation of gene expression. In all eukaryotes, mediator of RNA polymerase II transcription (Mediator), a large complex with modular organization, is generally required for transcription by RNA polymerase II, and it regulates various steps of this process. The main function of Mediator is to transduce signals from the transcription activators bound to enhancer regions to the transcription machinery, which is assembled at promoters as the preinitiation complex (PIC) to control transcription initiation. Recent functional studies of Mediator with the use of structural biology approaches and functional genomics have revealed new insights into Mediator activity and its regulation during transcription initiation, including how Mediator is recruited to transcription regulatory regions and how it interacts and cooperates with PIC components to assist in PIC assembly. Novel roles of Mediator in the control of gene expression have also been revealed by showing its connection to the nuclear pore and linking Mediator to the regulation of gene positioning in the nuclear space. Clear links between Mediator subunits and disease have also encouraged studies to explore targeting of this complex as a potential therapeutic approach in cancer and fungal infections.


Asunto(s)
Complejo Mediador/genética , Complejo Mediador/metabolismo , Transcripción Genética , Animales , Quinasa 8 Dependiente de Ciclina/antagonistas & inhibidores , Evolución Molecular , Regulación de la Expresión Génica , Humanos , Complejo Mediador/química , Modelos Biológicos , Modelos Genéticos , Micosis/genética , Micosis/metabolismo , Micosis/terapia , Neoplasias/genética , Neoplasias/metabolismo , Neoplasias/terapia , Poro Nuclear/genética , Poro Nuclear/metabolismo , ARN Polimerasa II/metabolismo , Secuencias Reguladoras de Ácidos Nucleicos , Transducción de Señal , Iniciación de la Transcripción Genética , Activación Transcripcional
11.
Nature ; 631(8020): 344-349, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38926575

RESUMEN

Many threats to biodiversity cannot be eliminated; for example, invasive pathogens may be ubiquitous. Chytridiomycosis is a fungal disease that has spread worldwide, driving at least 90 amphibian species to extinction, and severely affecting hundreds of others1-4. Once the disease spreads to a new environment, it is likely to become a permanent part of that ecosystem. To enable coexistence with chytridiomycosis in the field, we devised an intervention that exploits host defences and pathogen vulnerabilities. Here we show that sunlight-heated artificial refugia attract endangered frogs and enable body temperatures high enough to clear infections, and that having recovered in this way, frogs are subsequently resistant to chytridiomycosis even under cool conditions that are optimal for fungal growth. Our results provide a simple, inexpensive and widely applicable strategy to buffer frogs against chytridiomycosis in nature. The refugia are immediately useful for the endangered species we tested and will have broader utility for amphibian species with similar ecologies. Furthermore, our concept could be applied to other wildlife diseases in which differences in host and pathogen physiologies can be exploited. The refugia are made from cheap and readily available materials and therefore could be rapidly adopted by wildlife managers and the public. In summary, habitat protection alone cannot protect species that are affected by invasive diseases, but simple manipulations to microhabitat structure could spell the difference between the extinction and the persistence of endangered amphibians.


Asunto(s)
Anuros , Quitridiomicetos , Resistencia a la Enfermedad , Especies en Peligro de Extinción , Micosis , Refugio de Fauna , Animales , Anuros/inmunología , Anuros/microbiología , Anuros/fisiología , Temperatura Corporal/inmunología , Temperatura Corporal/fisiología , Temperatura Corporal/efectos de la radiación , Quitridiomicetos/inmunología , Quitridiomicetos/patogenicidad , Quitridiomicetos/fisiología , Resistencia a la Enfermedad/inmunología , Resistencia a la Enfermedad/fisiología , Resistencia a la Enfermedad/efectos de la radiación , Ecosistema , Micosis/veterinaria , Micosis/microbiología , Micosis/inmunología , Luz Solar , Animales Salvajes/inmunología , Animales Salvajes/microbiología , Animales Salvajes/fisiología , Especies Introducidas
12.
Nature ; 623(7989): 1079-1085, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37938782

RESUMEN

Decades of previous efforts to develop renal-sparing polyene antifungals were misguided by the classic membrane permeabilization model1. Recently, the clinically vital but also highly renal-toxic small-molecule natural product amphotericin B was instead found to kill fungi primarily by forming extramembraneous sponge-like aggregates that extract ergosterol from lipid bilayers2-6. Here we show that rapid and selective extraction of fungal ergosterol can yield potent and renal-sparing polyene antifungals. Cholesterol extraction was found to drive the toxicity of amphotericin B to human renal cells. Our examination of high-resolution structures of amphotericin B sponges in sterol-free and sterol-bound states guided us to a promising structural derivative that does not bind cholesterol and is thus renal sparing. This derivative was also less potent because it extracts ergosterol more slowly. Selective acceleration of ergosterol extraction with a second structural modification yielded a new polyene, AM-2-19, that is renal sparing in mice and primary human renal cells, potent against hundreds of pathogenic fungal strains, resistance evasive following serial passage in vitro and highly efficacious in animal models of invasive fungal infections. Thus, rational tuning of the dynamics of interactions between small molecules may lead to better treatments for fungal infections that still kill millions of people annually7,8 and potentially other resistance-evasive antimicrobials, including those that have recently been shown to operate through supramolecular structures that target specific lipids9.


Asunto(s)
Antifúngicos , Riñón , Polienos , Esteroles , Animales , Humanos , Ratones , Anfotericina B/análogos & derivados , Anfotericina B/química , Anfotericina B/toxicidad , Antifúngicos/química , Antifúngicos/metabolismo , Antifúngicos/farmacología , Antifúngicos/toxicidad , Células Cultivadas , Colesterol/química , Colesterol/metabolismo , Farmacorresistencia Fúngica , Ergosterol/química , Ergosterol/metabolismo , Riñón/efectos de los fármacos , Cinética , Pruebas de Sensibilidad Microbiana , Micosis/tratamiento farmacológico , Micosis/microbiología , Polienos/química , Polienos/metabolismo , Polienos/farmacología , Pase Seriado , Esteroles/química , Esteroles/metabolismo , Factores de Tiempo
13.
Immunol Rev ; 322(1): 28-52, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38069482

RESUMEN

Fungi are opportunists: They particularly require a defect of immunity to cause severe or disseminated disease. While often secondary to an apparent iatrogenic cause, fungal diseases do occur in the absence of one, albeit infrequently. These rare cases may be due to an underlying genetic immunodeficiency that can present variably in age of onset, severity, or other infections, and in the absence of a family history of disease. They may also be due to anti-cytokine autoantibodies. This review provides a background on how human genetics or autoantibodies underlie cases of susceptibility to severe or disseminated fungal disease. Subsequently, the lessons learned from these inborn errors of immunity marked by fungal disease (IEI-FD) provide a framework to begin to mechanistically decipher fungal syndromes, potentially paving the way for precision therapy of the mycoses.


Asunto(s)
Síndromes de Inmunodeficiencia , Micosis , Humanos , Genómica , Hongos , Autoanticuerpos
14.
N Engl J Med ; 390(12): 1105-1117, 2024 Mar 21.
Artículo en Inglés | MEDLINE | ID: mdl-38507753

RESUMEN

BACKGROUND: Autoantibodies against interleukin-12 (anti-interleukin-12) are often identified in patients with thymoma, but opportunistic infections develop in only some of these patients. Interleukin-12 (with subunits p40 and p35) shares a common subunit with interleukin-23 (subunits p40 and p19). In a patient with disseminated Burkholderia gladioli infection, the identification of both anti-interleukin-23 and anti-interleukin-12 prompted further investigation. METHODS: Among the patients (most of whom had thymoma) who were known to have anti-interleukin-12, we screened for autoantibodies against interleukin-23 (anti-interleukin-23). To validate the potential role of anti-interleukin-23 with respect to opportunistic infection, we tested a second cohort of patients with thymoma as well as patients without either thymoma or known anti-interleukin-12 who had unusual infections. RESULTS: Among 30 patients with anti-interleukin-12 who had severe mycobacterial, bacterial, or fungal infections, 15 (50%) also had autoantibodies that neutralized interleukin-23. The potency of such neutralization was correlated with the severity of these infections. The neutralizing activity of anti-interleukin-12 alone was not associated with infection. In the validation cohort of 91 patients with thymoma, the presence of anti-interleukin-23 was associated with infection status in 74 patients (81%). Overall, neutralizing anti-interleukin-23 was detected in 30 of 116 patients (26%) with thymoma and in 30 of 36 patients (83%) with disseminated, cerebral, or pulmonary infections. Anti-interleukin-23 was present in 6 of 32 patients (19%) with severe intracellular infections and in 2 of 16 patients (12%) with unusual intracranial infections, including Cladophialophora bantiana and Mycobacterium avium complex. CONCLUSIONS: Among patients with a variety of mycobacterial, bacterial, or fungal infections, the presence of neutralizing anti-interleukin-23 was associated with severe, persistent opportunistic infections. (Funded by the National Institute of Allergy and Infectious Diseases and others.).


Asunto(s)
Autoanticuerpos , Síndromes de Inmunodeficiencia , Interleucina-23 , Infecciones Oportunistas , Adulto , Humanos , Autoanticuerpos/inmunología , Síndromes de Inmunodeficiencia/inmunología , Interleucina-12/antagonistas & inhibidores , Interleucina-12/inmunología , Interleucina-23/antagonistas & inhibidores , Interleucina-23/inmunología , Micosis/inmunología , Infecciones Oportunistas/inmunología , Timoma/inmunología , Neoplasias del Timo/inmunología , Anticuerpos Neutralizantes/inmunología , Infecciones Bacterianas/inmunología
15.
Semin Immunol ; 67: 101751, 2023 05.
Artículo en Inglés | MEDLINE | ID: mdl-36989541

RESUMEN

Immunity to fungal infections of the central nervous system (CNS) is one of the most poorly understood subjects within the field of medical mycology. Yet, the majority of deaths from invasive fungal infections are caused by brain-tropic fungi. In recent years, there have been several significant discoveries in the regulation of neuroinflammation and the role of the immune system in tissue homeostasis within the CNS. In this review, I highlight five important advances in the neuroimmunology field over the last decade and discuss how we should capitalise on these discoveries to better understand the pathogenesis of fungal CNS infections. In addition, the latest insights into fungal invasion tactics, microglia-astrocyte crosstalk and regulation of antifungal adaptive immune responses are summarised in the context of our contemporary understanding of CNS-specific immunity.


Asunto(s)
Infecciones del Sistema Nervioso Central , Micosis , Humanos , Sistema Nervioso Central , Microglía , Inmunidad
16.
Semin Immunol ; 67: 101752, 2023 05.
Artículo en Inglés | MEDLINE | ID: mdl-37001464

RESUMEN

The continuous expansion of immunocompromised patient populations at-risk for developing life-threatening opportunistic fungal infections in recent decades has helped develop a deeper understanding of antifungal host defenses, which has provided the foundation for eventually devising immune-based targeted interventions in the clinic. This review outlines how genetic variation in certain immune pathway-related genes may contribute to the observed clinical variability in the risk of acquisition and/or severity of fungal infections and how immunogenetic-based patient stratification may enable the eventual development of personalized strategies for antifungal prophylaxis and/or vaccination. Moreover, this review synthesizes the emerging cytokine-based, cell-based, and other immunotherapeutic strategies that have shown promise as adjunctive therapies for boosting or modulating tissue-specific antifungal immune responses in the context of opportunistic fungal infections.


Asunto(s)
Antifúngicos , Micosis , Humanos , Antifúngicos/uso terapéutico , Inmunoterapia , Citocinas
17.
Semin Immunol ; 66: 101728, 2023 03.
Artículo en Inglés | MEDLINE | ID: mdl-36841146

RESUMEN

The respiratory tree maintains sterilizing immunity against human fungal pathogens. Humans inhale ubiquitous filamentous molds and geographically restricted dimorphic fungal pathogens that form small airborne conidia. In addition, pathogenic yeasts, exemplified by encapsulated Cryptococcus species, and Pneumocystis pose significant fungal threats to the lung. Classically, fungal pneumonia occurs in immune compromised individuals, specifically in patients with HIV/AIDS, in patients with hematologic malignancies, in organ transplant recipients, and in patients treated with corticosteroids and targeted biologics that impair fungal immune surveillance in the lung. The emergence of fungal co-infections during severe influenza and COVID-19 underscores the impairment of fungus-specific host defense pathways in the lung by respiratory viruses and by medical therapies to treat viral infections. Beyond life-threatening invasive syndromes, fungal antigen exposure can exacerbate allergenic disease in the lung. In this review, we discuss emerging principles of lung-specific antifungal immunity, integrate the contributions and cooperation of lung epithelial, innate immune, and adaptive immune cells to mucosal barrier immunity, and highlight the pathogenesis of fungal-associated allergenic disease. Improved understanding of fungus-specific immunity in the respiratory tree has paved the way to develop improved diagnostic, pre-emptive, therapeutic, and vaccine approaches for fungal diseases of the lung.


Asunto(s)
COVID-19 , Micosis , Humanos , Pulmón , Hongos , Inmunidad Innata
18.
Proc Natl Acad Sci U S A ; 121(4): e2317928121, 2024 Jan 23.
Artículo en Inglés | MEDLINE | ID: mdl-38236738

RESUMEN

Batrachochytrium dendrobatidis (Bd), a causative agent of chytridiomycosis, is decimating amphibian populations around the world. Bd belongs to the chytrid lineage, a group of early-diverging fungi that are widely used to study fungal evolution. Like all chytrids, Bd develops from a motile form into a sessile, growth form, a transition that involves drastic changes in its cytoskeletal architecture. Efforts to study Bd cell biology, development, and pathogenicity have been limited by the lack of genetic tools with which to test hypotheses about underlying molecular mechanisms. Here, we report the development of a transient genetic transformation system for Bd. We used electroporation to deliver exogenous DNA into Bd cells and detected transgene expression for up to three generations under both heterologous and native promoters. We also adapted the transformation protocol for selection using an antibiotic resistance marker. Finally, we used this system to express fluorescent protein fusions and, as a proof of concept, expressed a genetically encoded probe for the actin cytoskeleton. Using live-cell imaging, we visualized the distribution and dynamics of polymerized actin at each stage of the Bd life cycle, as well as during key developmental transitions. This transformation system enables direct testing of key hypotheses regarding mechanisms of Bd pathogenesis. This technology also paves the way for answering fundamental questions of chytrid cell, developmental, and evolutionary biology.


Asunto(s)
Quitridiomicetos , Micosis , Animales , Batrachochytrium , Quitridiomicetos/genética , Anuros , Anfibios/microbiología , Micosis/microbiología , Transformación Genética
19.
Proc Natl Acad Sci U S A ; 121(12): e2319582121, 2024 Mar 19.
Artículo en Inglés | MEDLINE | ID: mdl-38483998

RESUMEN

The presence of viruses that spread to both plant and fungal populations in nature has posed intriguingly scientific question. We found a negative-strand RNA virus related to members of the family Phenuiviridae, named Valsa mali negative-strand RNA virus 1 (VmNSRV1), which induced strong hypovirulence and was prevalent in a population of the phytopathogenic fungus of apple Valsa canker (Valsa mali) infecting apple orchards in the Shaanxi Province of China. Intriguingly, VmNSRV1 encodes a protein with a viral cell-to-cell movement function in plant tissue. Mechanical leaf inoculation showed that VmNSRV1 could systemically infect plants. Moreover, VmNSRV1 was detected in 24 out of 139 apple trees tested in orchards in Shaanxi Province. Fungal inoculation experiments showed that VmNSRV1 could be bidirectionally transmitted between apple plants and V. mali, and VmNSRV1 infection in plants reduced the development of fungal lesions on leaves. Additionally, the nucleocapsid protein encoded by VmNSRV1 is associated with and rearranged lipid droplets in both fungal and plant cells. VmNSRV1 represents a virus that has adapted and spread to both plant and fungal hosts and shuttles between these two organisms in nature (phyto-mycovirus) and is potential to be utilized for the biocontrol method against plant fungal diseases. This finding presents further insights into the virus evolution and adaptation encompassing both plant and fungal hosts.


Asunto(s)
Ascomicetos , Virus Fúngicos , Malus , Micosis , Virus ARN , Ascomicetos/genética , Virus ARN/genética , Enfermedades de las Plantas/microbiología , Malus/metabolismo
20.
PLoS Pathog ; 20(9): e1012430, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39264909

RESUMEN

To manage and treat chronic fungal diseases effectively, we require an improved understanding of their complexity. There is an increasing appreciation that chronic infection populations are often heterogeneous due to diversification and drift, even within a single microbial species. Genetically diverse populations can contribute to persistence and resistance to treatment by maintaining cells with different phenotypes capable of thriving in these dynamic environments. In chronic infections, fungal pathogens undergo prolonged challenges that can drive trait selection to convergent adapted states through restricted access to critical nutrients, assault by immune effectors, competition with other species, and antifungal drugs. This review first highlights the various genetic and epigenetic mechanisms that promote diversity in pathogenic fungal populations and provide an additional barrier to assessing the actual heterogeneity of fungal infections. We then review existing studies of evolution and genetic heterogeneity in fungal populations from lung infections associated with the genetic disease cystic fibrosis. We conclude with a discussion of open research questions that, once answered, may aid in diagnosing and treating chronic fungal infections.


Asunto(s)
Hongos , Micosis , Humanos , Hongos/genética , Hongos/patogenicidad , Micosis/microbiología , Micosis/inmunología , Variación Genética , Animales
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