In Vivo Virulence of<i>Candida albicans</i>Isolates Causing Mucosal Infections in People Infected with the Human Immunodeficiency Virus

Taylor, Brad N.; Fichtenbaum, Carl J.; Saavedra, Michael C.; Slavinsky, Joseph; Swoboda, Rolf; Wozniak, Karen L.; Arribas, Alfredo; Powderly, William G.; Fidel, Paul L.

doi:10.1086/315768

Cited by 34 publications

(31 citation statements)

References 15 publications

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“…It is noteworthy that C. albicans strains vary considerably in their ability to colonize mucosal sites (44,58). The gene expression pattern exhibited by strains with enhanced ability to colonize may differ in interesting ways from the pattern of gene expression observed in this study.…”

Section: Discussionmentioning

confidence: 56%

Adaptations of Candida albicans for Growth in the Mammalian Intestinal Tract

et al. 2010

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Section: Discussionmentioning

confidence: 56%

Adaptations of Candida albicans for Growth in the Mammalian Intestinal Tract

et al. 2010

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“…Candida colonization varies by both mucosal site and Candida species and strain (24,31). It is important to note that the differences between C. albicans strains are not well understood, and even Candida species show altered organ specificity during GI colonization, as demonstrated by Candida pintolopesii preferentially colonizing the murine stomach (2).…”

Section: Discussionmentioning

confidence: 99%

Candida albicans and Bacterial Microbiota Interactions in the Cecum during Recolonization following Broad-Spectrum Antibiotic Therapy

et al. 2012

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ABSTRACTCandida albicansis a normal member of the gastrointestinal (GI) tract microbiota of healthy humans, but during host immunosuppression or alterations in the bacterial microbiota,C. albicanscan disseminate and cause life-threatening illness. The bacterial microbiome of the GI tract, including lactic acid bacteria (LAB), plays a vital role in preventing fungal invasion. However, little is known about the role ofC. albicansin shaping the bacterial microbiota during antibiotic recovery. We investigated the fungal burdens in the GI tracts of germfree mice and mice with a disturbed microbiome to demonstrate the role of the microbiota in preventingC. albicanscolonization. Histological analysis demonstrated that colonization withC. albicansduring antibiotic treatment does not trigger overt inflammation in the murine cecum. Bacterial diversity is reduced long term following cefoperazone treatment, but the presence ofC. albicansduring antibiotic recovery promoted the recovery of bacterial diversity. Cefoperazone diminishesBacteroidetespopulations long term in the ceca of mice, but the presence ofC. albicansduring cefoperazone recovery promotedBacteroidetespopulation recovery. However, the presence ofC. albicansresulted in a long-term reduction inLactobacillusspp. and promotedEnterococcus faecalispopulations. Previous studies have focused on the ability of bacteria to alterC. albicans; this study addresses the ability ofC. albicansto alter the bacterial microbiota during nonpathogenic colonization.

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“…Also, the interaction between the immune system and MDR transporters in C. al-bicans may also extend to transporters of the major facilitator superfamily, since deletion of the CaMDR1 gene in C. albicans has been shown to result in reduced virulence (7). Finally, other studies have shown that the virulence of C. albicans strains does not appear to be related to their azole resistance status (5,70), although the molecular mechanism of azole resistance in these strains was not identified. It will be important to determine the capacity of multidrug transporters to modulate C. albicans virulence in animal models by using wellcharacterized strains engineered to overexpress such transporters individually or in combination in otherwise identical genetic backgrounds.…”

Section: Vol 47 2003mentioning

confidence: 97%

Functional Similarities and Differences between Candida albicans Cdr1p and Cdr2p Transporters

Gauthier

Weber

Alarco

et al. 2003

Antimicrob Agents Chemother

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The Candida albicans CDR1 and CDR2 genes code for highly homologous ATP-binding cassette (ABC) transporters which are overexpressed in azole-resistant clinical isolates and which confer resistance to multiple drugs by actively transporting their substrates out of the cells. These transporters are formed by two homologous halves, each with an intracellular domain containing an ATP-binding site followed by a membrane-associated domain. We have expressed Cdr1p and Cdr2p in Saccharomyces cerevisiae to investigate their functions. The two proteins were properly expressed and functional, as determined by Western blotting, drug susceptibility assays, and rhodamine efflux. Using total membrane proteins from these transformants, we showed that Cdr1p and Cdr2p bind to the photoreactive analogue of rhodamine 123, [125 I]iodoaryl azidorhodamine 123 (IAARh123). IAARh123 photoaffinity labeling of membranes prepared from cells expressing either the N half or the C half of Cdr2p, or both, demonstrated that both halves contribute to rhodamine binding and can bind to rhodamine independently. Interestingly, Cdr1p was found to confer hypersusceptibility to FK520, an immunosuppressant and antifungal agent, whereas Cdr2p conferred resistance to this compound, uncovering a major functional difference between the two transporters. Furthermore, when administered in combination with azoles, FK520 sensitized cells expressing CDR1 but not those expressing CDR2. Finally, we showed that Cdr2p confers hypersusceptibility to hydrogen peroxide and resistance to diamide, while Cdr1p has no effect against these oxidative agents. Taken together, our results demonstrate that, despite a high level of structural conservation, Cdr1p and Cdr2p exhibit major functional differences, suggesting distinct biological functions.Multidrug resistance (MDR) or pleiotropic drug resistance (PDR) is characterized by cellular cross-resistance to a broad spectrum of structurally and functionally unrelated cytotoxic compounds. It operates in a wide variety of cell types and involves the overexpression of membrane-associated transporters functioning as drug efflux pumps. Many of these transporters belong to the ATP-binding cassette (ABC) superfamily and contain highly conserved consensus sequences for ATP binding and hydrolysis (34). Well-characterized ABC transporters involved in MDR in mammalian cells include P glycoprotein type 1 (P-gp1) and the MDR-associated protein type 1 (MRP1), whose overexpression causes resistance to several anticancer drugs (2, 35). In the yeast Saccharomyces cerevisiae, overexpression of the ABC transporters Pdr5p and Snq2p has been shown to confer resistance to several different compounds with antifungal activities (6). Pdr5p and Snq2p are homologous proteins formed by two similar halves, each with an N-terminal hydrophilic domain that contains the ABC motif followed by a C-terminal hydrophobic domain with six predicted transmembrane (TM) segments, a structure characteristic of the PDR subfamily of ABC transporters ([ABC-TM] 2 ) (14, 67). ...

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In Vivo Virulence ofCandida albicansIsolates Causing Mucosal Infections in People Infected with the Human Immunodeficiency Virus

Cited by 34 publications

References 15 publications

Adaptations of Candida albicans for Growth in the Mammalian Intestinal Tract

Adaptations of Candida albicans for Growth in the Mammalian Intestinal Tract

Candida albicans and Bacterial Microbiota Interactions in the Cecum during Recolonization following Broad-Spectrum Antibiotic Therapy

Functional Similarities and Differences between Candida albicans Cdr1p and Cdr2p Transporters

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