Fungal endophytes which invade insect galls: insect pathogens,benign saprophytes,or fungal inquilines?

Fungi are frequently found within insect galls. However, the origin of these fungi, whether they are acting as pathogens, saprophytes invading already dead galls, or fungal inquilines which invade the gall but kill the gall maker by indirect means, is rarely investigated. A pathogenic role for these fungi is usually inferred but never tested. I chose the following leaf-galling-insect/host-plant pairs (1) a cynipid which forms two-chambered galls on the veins of Oregon white oak, (2) a cynipid which forms single-chambered galls on California coast live oak, and (3) an aphid which forms galls on narrowleaf cottonwood leaves. All pairs were reported to have fungi associated with dead insects inside the gall. These fungi were cultured and identified. For the two cynipids, all fungi found inside the galls were also present in the leaves as fungal endophytes. The cottonwood leaves examined did not harbor fungal endophytes. For the cynipid on Oregon white oak, the fungal endophyte grows from the leaf into the gall and infects all gall tissue but does not directly kill the gall maker. The insect dies as a result of the gall tissue dying from fungal infection. Therefore, the fungus acts as an inquiline. Approximately 12.5% of these galls die as a result of invasion by the fungal endophyte.     

Trichoderma/pathogen/plant interaction in pre-harvest food security

Large losses before crop harvesting are caused by plant pathogens, such as viruses, bacteria, oomycetes, fungi, and nematodes. Among these, fungi are the major cause of losses in agriculture worldwide. Plant pathogens are still controlled through application of agrochemicals, causing human disease and impacting environmental and food security. Biological control provides a safe alternative for the control of fungal plant pathogens, because of the ability of biocontrol agents to establish in the ecosystem. Some Trichoderma spp. are considered potential agents in the control of fungal plant diseases. They can interact directly with roots, increasing plant growth, resistance to diseases, and tolerance to abiotic stress. Furthermore, Trichoderma can directly kill fungal plant pathogens by antibiosis, as well as via mycoparasitism strategies. In this review, we will discuss the interactions between Trichoderma/fungal pathogens/plants during the pre-harvest of crops. In addition, we will highlight how these interactions can influence crop production and food security. Finally, we will describe the future of crop production using antimicrobial peptides, plants carrying pathogen-derived resistance, and plantibodies.     

Fungal factors involved in host immune evasion,modulation and exploitation during infection

Human and plant pathogenic fungi have a major impact on public health and agriculture. Although these fungi infect very diverse hosts and are often highly adapted to specific host niches, they share surprisingly similar mechanisms that mediate immune evasion, modulation of distinct host targets and exploitation of host nutrients, highlighting that successful strategies have evolved independently among diverse fungal pathogens. These attributes are facilitated by an arsenal of fungal factors. However, not a single molecule, but rather the combined effects of several factors enable these pathogens to establish infection. In this review, we discuss the principles of human and plant fungal pathogenicity mechanisms and discuss recent discoveries made in this field.     

Studying fungal pathogens of humans and fungal infections: fungal diversity and diversity of approaches

Seminal work by Louis Pasteur revealed the contribution of fungi – yeasts and microsporidia to agroindustry and disease in animals, respectively. More than 150 years later, the impact of fungi on human health and beyond is an ever-increasing issue, although often underestimated. Recent studies estimate that fungal infections, especially those caused by Candida, Cryptococcus and Aspergillus species, kill more than one million people annually. Indeed, these neglected infections are in general very difficult to cure and the associated mortality remains very high even when antifungal treatments exist. The development of new antifungals and diagnostic tools that are both necessary to fight fungal diseases efficiently, requires greater insights in the biology of the fungal pathogens of humans in the context of the infection, on their epidemiology, and on their role in the human mycobiota. We also need a better understanding of the host immune responses to fungal pathogens as well as the genetic basis for the increased sensitivity of some individuals to fungal infections. Here, we highlight some recent progress made in these different areas of research, in particular based on work conducted in our own laboratories. These progresses should lay the ground for better management of fungal infections, as they provide opportunities for better diagnostic, vaccination, the development of classical antifungals but also strategies for targeting virulence factors or the host.     

Interplay between Candida albicans and the Antimicrobial Peptide Armory

Antimicrobial peptides (AMPs) are key elements of innate immunity, which can directly kill multiple bacterial, viral, and fungal pathogens. The medically important fungus Candida albicans colonizes different host niches as part of the normal human microbiota. Proliferation of C. albicans is regulated through a complex balance of host immune defense mechanisms and fungal responses. Expression of AMPs against pathogenic fungi is differentially regulated and initiated by interactions of a variety of fungal pathogen-associated molecular patterns (PAMPs) with pattern recognition receptors (PRRs) on human cells. Inflammatory signaling and other environmental stimuli are also essential to control fungal proliferation and to prevent parasitism. To persist in the host, C. albicans has developed a three-phase AMP evasion strategy, including secretion of peptide effectors, AMP efflux pumps, and regulation of signaling pathways. These mechanisms prevent C. albicans from the antifungal activity of the major AMP classes, including cathelicidins, histatins, and defensins leading to a basal resistance. This minireview summarizes human AMP attack and C. albicans resistance mechanisms and current developments in the use of AMPs as antifungal agents.     

Genes Encoding Proteolytic Enzymes Fungalysin and Subtilisin in Dermatophytes of Human and Animal Origin: A Comparative Study

Mycopathologia - Dermatophytes are among the most successful fungal pathogens in humans, but their virulence mechanisms have not yet been fully characterized. Dermatophytic fungi secrete proteases...     

Immunoglobulins in defense, pathogenesis, and therapy of fungal diseases

Only two decades ago antibodies to fungi were thought to have little or no role in protection against fungal diseases. However, subsequent research has provided convincing evidence that certain antibodies can modify the course of fungal infection to the benefit or detriment of the host. Hybridoma technology was the breakthrough that enabled the characterization of antibodies to fungi, illuminating some of the requirements for antibody efficacy. As discussed in this review, fungal-specific antibodies mediate protection through direct actions on fungal cells and through classical mechanisms such as phagocytosis and complement activation. Although mechanisms of antibody-mediated protection are often species-specific, numerous fungal antigens can be targeted to generate vaccines and therapeutic immunoglobulins. Furthermore, the study of antibody function against medically important fungi has provided fresh immunological insights into the complexity of humoral immunity that are likely to apply to other pathogens.     

Characterisation of innate fungal recognition in the lung

The innate recognition of fungi by leukocytes is mediated by pattern recognition receptors (PRR), such as Dectin-1, and is thought to occur at the cell surface triggering intracellular signalling cascades which lead to the induction of protective host responses. In the lung, this recognition is aided by surfactant which also serves to maintain the balance between inflammation and pulmonary function, although the underlying mechanisms are unknown. Here we have explored pulmonary innate recognition of a variety of fungal particles, including zymosan, Candida albicans and Aspergillus fumigatus, and demonstrate that opsonisation with surfactant components can limit inflammation by reducing host-cell fungal interactions. However, we found that this opsonisation does not contribute directly to innate fungal recognition and that this process is mediated through non-opsonic PRRs, including Dectin-1. Moreover, we found that pulmonary inflammatory responses to resting Aspergillus conidia were initiated by these PRRs in acidified phagolysosomes, following the uptake of fungal particles by leukocytes. Our data therefore provides crucial new insights into the mechanisms by which surfactant can maintain pulmonary function in the face of microbial challenge, and defines the phagolysosome as a novel intracellular compartment involved in the innate sensing of extracellular pathogens in the lung.     

Evolution of antifungal-drug resistance: mechanisms and pathogen fitness

Like other microorganisms, fungi exist in populations that are adaptable. Under the selection imposed by antifungal drugs, drug-sensitive fungal pathogens frequently evolve resistance. Although the molecular mechanisms of resistance are well-characterized, there are few measurements of the impact of these mechanisms on pathogen fitness in different environments. To predict resistance before a new drug is prescribed in the clinic, the full spectrum of potential resistance mutations and the interactions among combinations of divergent mechanisms can be determined in evolution experiments. In the search for new strategies to manage drug resistance, measuring the limits of adaptation might reveal methods for trapping fungal pathogens in evolutionary dead ends.     

Fungal Pathogens in CF Airways: Leave or Treat?

Chronic airway infection plays an essential role in the progress of cystic fibrosis (CF) lung disease. In the past decades, mainly bacterial pathogens, such as Pseudomonas aeruginosa, have been the focus of researchers and clinicians. However, fungi are frequently detected in CF airways and there is an increasing body of evidence that fungal pathogens might play a role in CF lung disease. Several studies have shown an association of fungi, particularly Aspergillus fumigatus and Candida albicans, with the course of lung disease in CF patients. Mechanistically, in vitro and in vivo studies suggest that an impaired immune response to fungal pathogens in CF airways renders them more susceptible to fungi. However, it remains elusive whether fungi are actively involved in CF lung disease pathologies or whether they rather reflect a dysregulated airway colonization and act as microbial bystanders. A key issue for dissecting the role of fungi in CF lung disease is the distinction of dynamic fungal–host interaction entities, namely colonization, sensitization or infection. This review summarizes key findings on pathophysiological mechanisms and the clinical impact of fungi in CF lung disease.     

昆虫天然免疫反应分子机制研究进展

昆虫体内缺乏高等脊椎动物所具有的获得性免疫系统, 只能依赖发达的天然免疫系统抵抗细菌、 真菌、 病毒等外源病原物的侵染。本文概括了昆虫天然免疫反应发生和作用的分子机制相关进展, 重点阐述了重要免疫相关因子在昆虫天然免疫反应中的功能和作用机制。昆虫天然免疫反应分为体液免疫和细胞免疫两种, 二者共同作用完成对病原物的吞噬 (phagocytosis)、 集结 (nodulation)、 包囊 (encapsulation)、 凝结 (coagulation)和黑化（melanization）等。当昆虫受到外界病原物的侵染时, 首先通过体内的模式识别蛋白（pattern recognition proteins/receptor, PRPs）识别并结合病原物表面特有的模式分子（pathogen-associated molecular pattern, PAMPs）, 继而一系列包括丝氨酸蛋白酶和丝氨酸蛋白酶抑制剂在内的级联激活反应被激活和调控, 产生抗菌肽、 黑色素等免疫效应分子, 清除或杀灭外源物。抗菌肽是一类小分子量的阳离子肽, 具有广谱抗菌活性, 针对不同类型的病原物, 抗菌肽的产生机制也不尽相同。昆虫体内存在着两种信号转导途径调节抗菌肽的产生： 一是由真菌和大部分革兰氏阳性菌激活的Toll途径; 二是由革兰氏阴性菌激活的Imd途径（immune deficiency pathway）。这两个途径通过激活不同转录因子调控不同抗菌肽基因的表达参与昆虫体内的天然免疫反应。     

The arms race continues: battle strategies between plants and fungal pathogens

Plants are under constant attack by a vast array of pathogens. To impede their attackers they use both broad-spectrum and pathogen-specific defence mechanisms. The arms race between plants and fungal pathogens is fascinatingly varied, and what might be elicited as a plant defence mechanism against a pathogen could promote or enhance the virulence of other pathogens. Fungi use countermeasures to detoxify plant antimicrobial compounds and to evade host resistance mechanisms. Certain fungal species also manipulate the host hormone balance to create an environment that is beneficial to their survival. Several lines of evidence indicate a co-evolutionary arms race in which both plants and fungi can respond to changes that occur in their opponents.     

The different morphologies of yeast and filamentous fungi trigger distinct killing and feeding mechanisms in a fungivorous amoeba

Size and diverse morphologies pose a primary challenge for phagocytes such as innate immune cells and predatory amoebae when encountering fungal prey. Although filamentous fungi can escape phagocytic killing by pure physical constraints, unicellular spores and yeasts can mask molecular surface patterns or arrest phagocytic processing. Here, we show that the fungivorous amoeba Protostelium aurantium was able to adjust its killing and feeding mechanisms to these different cell shapes. Yeast-like fungi from the major fungal groups of basidiomycetes and ascomycetes were readily internalized by phagocytosis, except for the human pathogen Candida albicans whose mannoprotein coat was essential to escape recognition by the amoeba. Dormant spores of the filamentous fungus Aspergillus fumigatus also remained unrecognized, but swelling and the onset of germination induced internalization and intracellular killing by the amoeba. Mature hyphae of A. fumigatus were mostly attacked from the hyphal tip and killed by an actin-mediated invasion of fungal filaments. Our results demonstrate that predatory pressure imposed by amoebae in natural environments selects for distinct survival strategies in yeast and filamentous fungi but commonly targets the fungal cell wall as a crucial molecular pattern associated to prey and pathogens.     

Entomopathogenic fungi and insect behaviour: from unsuspecting hosts to targeted vectors

The behavioural response of an insect to a fungal pathogen will have a direct effect on the efficacy of the fungus as a biological control agent. In this paper we describe two processes that have a significant effect on the interactions between insects and entomopathogenic fungi: (a) the ability of target insects to detect and avoid fungal pathogens and (b) the transmission of fungal pathogens between host insects. The behavioural interactions between insects and entomopathogenic fungi are described for a variety of fungal pathogens ranging from commercially available bio-pesticides to non-formulated naturally occurring pathogens. The artificial manipulation of insect behaviour using dissemination devices to contaminate insects with entomopathogenic fungi is then described. The implications of insect behaviour on the use of fungal pathogens as biological control agents are discussed.     

Using fungi and yeasts to manage vegetable crop diseases

Vegetable crops are grown worldwide as a source of nutrients and fiber in the human diet. Fungal plant pathogens can cause devastation in these crops under appropriate environmental conditions. Vegetable producers confronted with the challenges of managing fungal pathogens have the opportunity to use fungi and yeasts as biological control agents. Several commercially available products have shown significant disease reduction through various mechanisms to reduce pathogen development and disease. Production of hydrolytic enzymes and antibiotics, competition for plant nutrients and niche colonization, induction of plant host defense mechanisms, and interference with pathogenicity factors in the pathogen are the most important mechanisms. Biotechnological techniques are becoming increasingly valuable to elucidate the mechanisms of action of fungi and yeasts and provide genetic characterization and molecular markers to monitor the spread of these agents.     

Interactions of fungi with phagocytes

Recent advances have broadened our knowledge of the unique role that dendritic cells, macrophages and neutrophils play in protecting the host against fungal infections and the mechanisms by which fungal pathogens attempt to subvert phagocytic defenses. In this article, the interplay between phagocytes and fungi is reviewed.     

Mechanisms of immune evasion in fungal pathogens

The incidence of life-threatening fungal infections has continued to increase in recent years, predominantly in patients debilitated by iatrogenic interventions or immunological dysfunctions. While the picture of the immunology of fungal infections grows increasingly complex, it is clear that the phagocyte-pathogen interaction is a critical determinant of establishing an infection. About 10 years ago, genome-scale approaches began to elucidate the intricate and extensive fungal response to phagocytosis and in the last few years it has become clear that some of this response actively modulates immune cell function. Fungal pathogens avoid detection by masking pathogen-associated molecular patterns, such as cell wall carbohydrates, and by downregulating the complement cascade. Once detected, various species interfere with phagocytosis and intracellular trafficking, and can repress production of antimicrobials like nitric oxide (NO). For the most part, the molecular mechanisms behind these behaviors are not yet known. This review discusses recent discoveries and insights into how fungi manipulate the host-pathogen interaction.     

Genomes, free radicals and plant cell invasion: recent developments in plant pathogenic fungi

This review describes current advances in our understanding of fungal-plant interactions. The widespread application of whole genome sequencing to a diverse range of fungal species has allowed new insight into the evolution of fungal pathogenesis and the definition of the gene inventories associated with important plant pathogens. This has also led to functional genomic approaches to carry out large-scale gene functional analysis. There has also been significant progress in understanding appressorium-mediated plant infection by fungi and its underlying genetic basis. The nature of biotrophic proliferation of fungal pathogens in host tissue has recently revealed new potential mechanisms for cell-to-cell movement by invading pathogens.