1210 Biochemical Society Transactions (2005) Volume 33, part 5 Azole susceptibility and resistance in Candida dubliniensis E. Pinjon 1 , G.P. Moran, D.C. Coleman and D.J. Sullivan Microbiology Research Unit, Division of Oral Biosciences, School of Dental Science and Dublin Dental Hospital, University of Dublin, Trinity College, Dublin 2, Republic of Ireland Abstract Candida dubliniensis is a recently described species of pathogenic yeast that shares many phenotypic features with Candida albicans. It is primarily associated with oral colonization and infection in HIV-infected individuals. Isolates of C. dubliniensis are generally susceptible to commonly used azole antifungal agents; however, resistance has been observed in clinical isolates and can be induced by in vitro exposure. Molecular mechanisms of azole resistance in C. dubliniensis include increased drug efflux, modifications of the target enzyme and alterations in the ergosterol biosynthetic pathway. Introduction Several species of the genus Candida form part of the normal oropharyngeal and gastrointestinal flora; however, they can become opportunistic pathogens and establish infections when host defences are impaired. Such infections range from superficial infections of the skin and mucous membranes to life-threatening invasive infections of the blood and/or or- gans. Having emerged as significant human pathogens during the past 2 decades, Candida species are frequently quoted as the fourth most common cause of nosocomial blood- stream infection in the U.S.A., with an associated mortality rate of 40–60%. The emergence of Candida species as significant human pathogens has been part of a general in- crease in the number of infections caused by fungal pathogens during the last 20 years. This shift in the epidemiology of fungal infections has been correlated with the increase in the number of immunocompromised and immunosuppressed patients, as well as with an increase in the use of invasive medi- cal procedures, in-dwelling central venous catheters and broad-spectrum antibiotics. Candida albicans is the most pathogenic Candida species and is the most common cause of Candida infections. However, over the last 2 decades, since the introduction and widespread use of the azole drugs fluconazole and itraconazole, other Candida species have emerged as significant pathogens of clinical importance [1]. This review focuses on one of these species, Candida dubliniensis, with particular emphasis on its resistance mechanisms to azole antifungal agents. Key words: azole, Candida dubliniensis, epidemiology, fluconazole, susceptibility, resistance mechanism. Abbreviations used: Cd, Candida dubliniensis; Cdr1p, Candida drug resistance protein 1; Mdr1p, multidrug resistance protein 1; MIC, minimum inhibitory concentration. 1 To whom correspondence should be addressed (email emmanuelle.pinjon@dental. tcd.ie). A recently described species: Candida dubliniensis In the early 1990s, several authors reported the recovery of atypical isolates of C. albicans from HIV-infected indi- viduals [2,3]. Although these isolates shared many features characteristic of C. albicans, they exhibited a number of atypi- cal properties. These atypical isolates possessed the ability to form germ tubes and abundant chlamydospores [4]. How- ever, they grew poorly or not at all at 42 ◦ C, unlike C. albicans isolates which grow well at this temperature. An extensive study of the phenotypic and genotypic characteristics of atyp- ical isolates recovered from the oral cavities of HIV-infected patients in Ireland and Australia, together with a phylo- genetic analysis of nucleotide sequences of the V3 region of the large rRNA subunit gene, demonstrated that the atypical isolates constituted a novel distinct taxon within the genus Candida for which the name C. dubliniensis was proposed [4]. Epidemiology of C. dubliniensis Since its identification in 1995, numerous studies have re- ported the recovery of C. dubliniensis isolates from a wide range of anatomical sites and clinical settings all over the world [5–8]. Despite its phenotypic similarities with C. albi- cans, C. dubliniensis appears to be a rare constituent of the normal oral and vaginal microbial flora. In a study of an Irish population, only 3.5% of normal healthy individuals were found to carry C. dubliniensis in the oral cavity [9]. How- ever, C. dubliniensis is commonly associated with oro- pharyngeal candidosis in HIV-infected and AIDS patients [10,11]. A high prevalence (15–30%) of C. dubliniensis in the oral cavities of HIV-infected and AIDS patients has been reported in several studies [9,11,12]. In a study on the prevalence of C. dubliniensis in the oral cavity in an Irish population, 26% of HIV-infected and 32% of AIDS patients C  2005 Biochemical Society