CAINFECTOME

Unravelling the infectome of Candida albicans

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 Obiettivo del progetto (Objective)

'The opportunistic human fungal pathogen, Candida albicans causes a wide range of serious disease manifestations, especially in individuals with an impaired immune system. The ability of C. albicans to successfully infect almost every anatomical niche of the human host is both a serious medical problem and an interesting biological property. It is known from in vitro transcriptional profiling that the organism rapidly alters gene expression in response to changing environments; however, very little is known of gene expression patterns in vivo. In addition, a significant proportion of C. albicans genes expressed during infection have no known function. This study will address these two problems in the following ways. Firstly, the transcriptional profile of C. albicans interaction with the host during three distinct models of infection (oral, liver and blood) will be analysed to determine whether C. albicans responds using general transcriptional mechanisms during infection or whether responses are specific depending on the anatomical niche. This transcriptional analysis will then form the basis of a systematic disruption strategy to elucidate the function and role of unknown function genes. Relevant deletion mutants will be generated using a rapid PCR based method and tested for host-interaction using established models of infection. This characterisation will elucidate the function of unknown function genes during infection and describe de novo properties of C. albicans biology. Furthermore, by testing mutants in more than one model of infection it will be shown whether a gene upregulated specifically during one type of infection has significance in another.'

Introduzione (Teaser)

Patients with impaired immune systems can be vulnerable to serious infection from the fungus Candida albicans. An EU-funded project has investigated how the infection is caused and how it can be treated.

Descrizione progetto (Article)

Infection depends upon a number of factors, although exactly how the fungus causes disease has not been clearly understood, until now. One of the main factors behind C. albicans virulence is its ability to grow both as ovoid yeast cells and as long, branching filamentous structures called hyphae.

The 'Unravelling the infectome of Candida albicans' (Cainfectome) project has identified new molecular mechanisms that can contribute to the microorganism's ability to cause infection. Research has involved the analysis of models of oral, liver and blood infection. The models have successfully identified aspects of gene expression during infection.

Project partners selected a set of 40 previously uncharacterised genes involved in infection and removed genes of interest through targeted deletion. The result has been the creation of a set of infection-associated gene deletion mutants. The mutant set was then screened for the potential ability to cause disease in two infection models.

Data from the Cainfectome project will help scientists understand how C. albicans rapidly alters the way its genes are expressed in response to a changing environment. In so doing, the initiative will enable EU scientists to provide an answer to this serious medical problem.