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Emergence of Saccharomyces cerevisiae as a human pathogen: Implications for biotechnology

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Abstract

The yeast Saccharomyces cerevisiae is widely used in baking, brewing, wine making, and biotechnology and previously has had GRAS (generally regarded as safe) status. Recent evidence indicates the involvement of S. cerevisiae in a range of superficial and systemic diseases. Numerous cases of S. cerevisiae-induced vaginitis have been documented as have cases of oropharyngeal infection. Potentially fatal systemic disease due to S. cerevisiae has been recorded in bone marrow transplant patients and in those immunocompromised as a result of cancer or AIDS. A number of studies have indicated that commercially available strains of S. cerevisiae may cause disease in certain individuals. Pathogenic isolates exhibit the ability to grow at 42°C, produce proteinase, and are capable of pseudohyphal growth. In addition, a number of isolates are capable of phenotypic switching and show partial or complete resistance to commonly used antifungal agents, including fluconazole. In the light of these findings, S. cerevisiae should now be regarded as an opportunistic pathogen, albeit of relatively low virulence, and treated accordingly by those in the industrial and biotechnological sectors.

Section snippets

Saccharomyces cerevisiae: friend or foe?

The saprophytic yeast S. cerevisiae is widely distributed in nature and has been used extensively since the dawn of civilization. Until recent times the primary use of this yeast has been in the production of bread (baker’s yeast) and alcoholic beverages (brewer’s yeast). It is also frequently ingested as a dietary supplement or inadvertently as a contaminant of food products.

S. cerevisiae has become increasingly important over recent years in biotechnology and is now one of the most studied

S. cerevisiae-induced disease

Although frequently encountered as a harmless body, commensal S. cerevisiae has been implicated in the induction of disease in a number of instances. It would appear that S. cerevisiae is exploiting the increased numbers of patients immunocompromised as a result of disease or therapy rather than exhibiting enhanced levels of virulence. A review of the medical literature indicates that S. cerevisiae isolates have been responsible for a variety of diseases ranging from superficial to

Superficial S. cerevisiae disease

Yeast-induced vaginitis affects approximately 75% of women at some point in their life, and a subpopulation of between 5% and 12% suffer from recurrent bouts of infection that may persist for months or, in severe cases, years [11]. Candida albicans is responsible for 85–90% of cases of this condition, with the remaining cases being due to a range of other Candida species. In a survey of the yeasts responsible for this condition in 2000 women, S. cerevisiae was identified as the causative agent

Systemic S. cerevisiae disease

S. cerevisiae-induced vaginitis may be unpleasant, and at times difficult to treat due to the inherent drug resistance of certain isolates, but it is not life threatening except in severely immunocompromised patients where systemic infection may result. Systemic fungal disease due to S. cerevisiae has been recorded occasionally and is most frequently found in severely ill patients and may be a contributer to, or in some cases the main cause of, death. S. cerevisiae has been implicated in

Virulence attributes of pathogenic S. cerevisiae isolates

Virulent isolates have been defined as those isolates of S. cerevisiae that are capable of growth at 42°C [26]. This is considered an important characteristic as febrile patients can manifest this temperature, and any organism that can survive and grow at this elevated temperature would have an inherent advantage. In an examination of a range of laboratory and industrial strains of S. cerevisiae, growth was observed over the range 37–40°C, but only virulent isolates were capable of growth at

Therapy for the control of S. cerevisiae disease

There are two major classes of antifungal agents: the polyenes and the azoles. Amphotericin B desoxycholate is the primary polyene for use against fungal infections and is produced by the Streptomyces. It is quite similar to a phospholipid in structure and length except that it contains a polyene hydrocarbon backbone as well as a polyhydroxyl backbone [34]. The drug is poorly soluble in water [35] due to the opposite polarities of the hydroxyls and hydrocarbons [34] and is conventionally

Drug resistance in pathogenic S. cerevisiae isolates

A range of antifungal agents have been used to treat S. cerevisiae infections and, in many cases, therapy has been unsuccessful. Underlying disease is possibly a factor preventing successful therapy [23]. The worldwide spread of HIV infection has brought about a large population of individuals susceptible to a wide variety of organisms, many of which had previously been regarded as nonpathogenic [44]. During the late 1980s and early 1990s, it was noted that many emerging fungal pathogens such

Implications for biotechnology

Although classically considered to be nonpathogenic, S. cerevisiae is now emerging as a cause of disease in immunocompromised patients [7], [8], [9]. A number of the virulence factors associated with clinical isolates of this yeast have been identified and partly characterized. It is generally agreed that the factors already described are only part of the overall complement of such factors, and the role of these in the pathogenicity of this yeast is poorly understood [26]. The work cited here

Conclusion

Although widely used for the production of bread and alcoholic beverages for thousands of years, S. cerevisiae is now being identified as an opportunistic pathogen in a number of cases. Those most at risk appear to be immunocompromised individuals but also patients showing no obvious predisposing factor and those working with the yeast on a regular basis. Although those isolates that have been implicated in disease have a number of clearly defined virulence characteristics, there remains the

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