This issue of the Mycologist contains four contemporary reviews of topical issues in the field of medical mycology – a branch of mycology that has been fuelled by the urgent need to discover new classes of antifungal drugs and which has benefited from the injection of new information from genome sequencing of key pathogens. These four vignettes are not intended to provide a coherent overview of medical mycology, but instead illustrate why that area of mycology is enjoying a period of investment, progress and academic excitement. The reviews are presented by four scientists who are the foremost authorities in their respective fields. They focus on drug discovery and drug resistance, and on recent advances in our understanding of the biology of the two major fungal pathogens of humans – Candida albicans and Aspergillus fumigatus.

Since the 1950s, antifungal drug discovery has identified three classes of natural products (griseofulvin, polyenes and echinocandins) and four classes of synthetic chemicals (allylamines, azoles, flucytosine and phenylmorpholines) with clinical value against fungal infections. For life threatening fungal disease, the polyene amphotericin B is still a common choice despite toxic side-effects. The azoles remain the most widely used group of anti fungals active against a wide range of mycoses, benefiting from creative chemistry to boost their effectiveness. More recently, the echinocandins show great promise, with caspofungin licensed for clinical use in 2002 and two other molecules close to registration. New advances in molecular genetics afford the promise of revealing new antifungal targets, together with new agents to inhibit those targets specifically.

Aspergillus fumigatus is the most common and life-threatening aerial fungal pathogen, especially among immunocompromised hosts. Understanding the pathobiology of this pathogen requires investigations both to characterise the immunosuppressive status of the phagocytic cells that usually kill the fungus in the immunocompetent host, and to identify fungal virulence factors that either promote the resistance of conidia to innate immunity or stimulate mycelial growth in the lung parenchyma. Recent findings are presented in this review and show how little we know of the interactions between host and pathogen. Now the genome of A. fumigatus has been sequenced, transcriptome/ proteome-based studies should disclose the multiple facets of A. fumigatus pathogenicity.

Recently, it was demonstrated that Candida albicans contains mating type genes. Since that discovery, it has been demonstrated that the majority of strains contain both a and "[agr ]" a genes, that a minority are homozygous for a or "[agr ]" and can undergo fusion, and that the cytological stages of fusion and zygote development are similar to the stages of mating in Saccharomyces cerevisiae. However, it has recently been demonstrated that in order to mate, homozygous a and homozygous "[agr ]" cells must undergo phenotypic switching from the white to opaque phase, adding a developmental step to mating that might be related to pathogenesis.

Fungal pathogens are using several mechanisms to circumvent the inhibitory actions of antifungal drugs. The variety of these mechanisms was revealed in recent years by several laboratories with molecular approaches. Besides the identification of genes involved in antifungal drug resistance and the discovery of alternative pathways of resistance (i.e. biofilm formation), novel concepts in the understanding of the survival of fungal pathogen in the presence of antifungal drug (antifungal tolerance) have emerged.

The two previous parts to this review have emphasised the relatively small number of mould toxins, associated with the mould genera Penicillium, Aspergillus and Fusarium, which may have the greatest impact in the context of human foods. There are, however, a large number of toxic mould metabolites, produced by a diverse range of other mould genera, with an extraordinary diversity of chemical structure and biological activity. The chemical structures are fascinating and worth studying because they provide clues about biosynthetic pathways and possible biological activity. The moulds producing them occur in a wide range of ecological niches from endophytes, obligate plant pathogens to saprophytes. This diversity will be explored from two points of view – damp houses and animal pastures.

Anyone who followed the developing epidemic of Severe Acute Respiratory Syndrome (SARS) in the media would be in little doubt as to the threat posed by new and unexpected diseases. Whilst the general public is probably more familiar with the various ′exotic′ viruses that have emerged in the past thirty years, medical mycology also has its own share of important emergent pathogens. In a regional context the most important of these is Penicillium marneffei Segratin et. al. – the causative agent of penicilliosis. This has become a very important complication in AIDS patients in large parts of the Far East, particularly in Thailand, Southern China and Hong Kong. Unlike more familiar fungal pathogens, such as Candida albicans and Aspergillus fumigatus, P. marneffei has only a short history – indeed it was first described as recently as the mid-1950s.

This photograph appeared in the Cambridge Evening News in September 2002 under the caption: “Giant … the garden's Jane Grimes with a Rigidoporus ulmarius nearly 5 m in circumference”. This reminded me that I had earlier been shown another very large specimen of this fungus in Kew Gardens. On contacting Alick Henrici as to this specimen in July 2003, he informed me that the Kew fungus had appeared some years ago in the Guinness Book of Records. In the 1995 edition of this work it was entered as the Largest Tree Fungus, measuring (in 1992) 150 x 144 cm with a circumference of 454 cm, and in the 1999 edition, measured in 1995, the size was recorded as 163 x 140 cm with a circumference of 480 cm. This meant that the Cambridge specimen might be of world class, so Jane, with arborist David Franklin and myself forthwith went to measure it. Our results showed it a worthy contender but less large at 150 x 133 cm diameter and 425 cm circumference.