Immunity to fungal infections

Fungal diseases represent an important paradigm in immunology, as they can result from either a lack of recognition by the immune system or overactivation of the inflammatory response. Research in this field is entering an exciting period of transition from studying the molecular and cellular bases of fungal virulence to determining the cellular and molecular mechanisms that maintain immune homeostasis with fungi. The fine line between these two research areas is central to our understanding of tissue homeostasis and its possible breakdown in fungal infections and diseases. Recent insights into immune responses to fungi suggest that functionally distinct mechanisms have evolved to achieve optimal host-fungus interactions in mammals.     

Immunity to fungal infections

The topic of immunity to fungal infections is of interest to a wide range of disciplines, from microbiology to immunology. It is of particular interest in terms of therapy of HIV-infected individuals, and patients with cancer or individuals who have received transplants. Understanding the nature and function of the immune response to fungi is an exciting challenge that might set the stage for new approaches to the treatment of fungal diseases, from immunotherapy to vaccines. The past decade has witnessed the development of a wide range of new approaches to elucidate events that occur at the host-fungus interface.     

Genomic approaches to fungal pathogenicity

Within a few years, the genome sequences of a large number of medically and agriculturally important fungi will be known. With this resource come the promises of genomic approaches to study pathogenicity and host-fungus interactions. Genomics is particularly attractive for these questions, as conventional genetic and biochemical approaches are limited in many pathogenic fungi. Recent work has applied signature-tagged mutagenesis and DNA microarray analysis to virulence studies in several fungal species, and novel approaches, such as protein arrays and genomic deletion libraries, are being developed in Saccharomyces cerevisiae and have significant potential in other fungi. High-throughput gene-discovery approaches should greatly increase our understanding of fungal pathogenesis.     

New approaches to augment fungal biotransformation

The possibility of using solid supports and intermittent substrate feeding to manipulate biotransformation by fungi was examined, with amoxapine as a model compound. Cunninghamella elegans ATCC 8688a grown as free cells in six-well plates showed 7-hydroxyamoxapine as the major metabolite of amoxapine biotransformation. However, when cells were grown in the presence of activated carbon, N-formyl-7-hydroxyamoxapine was formed as the major metabolite. Intermittent feeding of amoxapine also favored the formation of N-formyl-7-hydroxyamoxapine.     

The fungal threat to global food security

Fungi threaten the security of food supply to human populations on several fronts. They destroy up to 30 % of crop products through disease and spoilage processes, while mycotoxin-producing fungi and opportunistic pathogens endanger food safety. Control of these fungi is vital for improving food security, but current measures are inadequate and further challenges due to human-population growth and climate change are escalating. Investment and innovation in research on strategies to control fungal growth, harnessed through international, inter-disciplinary collaboration across socio-economic boundaries, provides one key to rising to this challenge.     

涉及临床各科的侵袭性真菌感染

真菌数量大、种类多、分布广。真菌感染因菌种的毒力、感染途径和宿主免疫状态等差异而出现不同的临床表现,临床各科医生都会遇到真菌病患者。真菌病的诊断取决于在病变组织内发现病原真菌成分如菌丝和(或)孢子。从病变组织中分离出真菌是菌种鉴定前提,也是抗真菌治疗的依据。“重视临床、强调菌学”是医学真菌研究的基本思路。真菌学家应该在联系临床与实验室中起关键作用。     

Use of non-pathogenic or hypovirulent fungal strains to protect plants against closely related fungal pathogens

Nonpathogenic (avirulent), or low virulent (hypovirulent) strains are capable of colonizing infection site niches on the plants' surfaces and protecting susceptible plants against their respective pathogens. Such phenomena have been demonstrated for a considerable number of plant pathogens. The modes of protection differ among the nonpathogenic strains, and one strain can protect by more than one mechanism. Competition for infection sites, or for nutrients (such as carbon, iron) as well as induction of the host plant resistance, have been demonstrated for several pathogens such as Rhizoctonia spp., Fusarium spp. and Pythium spp. Mycoparasitism was shown for Pythium spp. Transmission of double stranded RNA mycoviruses from hypovirulent strains to virulent strains renders the virulent strains hypovirulent. Chestnut trees infected with the chestnut blight pathogen, Cryphonectria (Endothia) parasitica, recovered after inoculation with transmissible hypovirulent strains. Nonpathogenic strains of various fungi are potential candidates for development of biocontrol preparations. Some strains are already used in Agriculture.     

Formate-forming fungal catabolic pathway to supply electrons to nitrate respiration

Pyruvate was catabolized anaerobically by resting cells of Fusarium oxysporum to form formate and acetate. Addition of nitrate decreased the accumulation of formate in the medium with concomitant formation of nitrite and N2O. The results suggested a unique metabolic pathway that occurs in fungi mediated by pyruvate-formate lyase to supply electrons via formate to fungal denitrification.     

Crowded locusts produce hatchlings vulnerable to fungal attack

Transgenerational effects of parental experience on offspring immunity are well documented in the vertebrate literature (where antibodies play an obligatory role), but have only recently been described in invertebrates. We have assessed the impact of parental rearing density upon offspring disease resistance by challenging day-old locust hatchlings (Schistocerca gregaria) from either crowd- or solitary-reared parents with the fungal pathogen Metarhizium anisopliae var. acridum. When immersed in standardized conidia suspensions, hatchlings from gregarious parents suffered greater pathogen-induced mortality than hatchlings from solitary-reared parents. This observation contradicts the basic theory of positive density-dependent prophylaxis and demonstrates that crowding has a transgenerational influence upon locust disease resistance.     

Genetically engineered resistance to bacterial and fungal pathogens

In the past 10 years, different strategies have been used to produce transgenic plants that are less susceptible to diseases caused by phytopathogenic fungi and bacteria. Genes from different organisms, including bacteria, fungi and plants, have been successfully used to develop these strategies. Some strategies have been shown to be effective against different pathogens, whereas others are specific to a single pathogen or even to a single pathovar or race of a given pathogen. In this review, we present the strategies that have been employed to produce transgenic plants less susceptible to bacterial and fungal diseases and which constitute an important area of plant biotechnology.The authors are with the Departamento de Ingeniería Genética de Plantas. Centro de Investigación y de Estudios Avanzados del IPN-Unidad Irapuato, Km 9.6 del Libramiento Norte carretera Irapuato-León, Apdo Postal 629, Irapuato, Mexico.