Candida albicans drug resistance – another way to cope with stress

Cannon, Richard D.; Lamping, Erwin; Holmes, Ann R.; Niimi, Kyoko; Tanabe, Koichi; Niimi, Masakazu; Monk, Brian C.

doi:10.1099/mic.0.2007/010405-0

Cited by 197 publications

(150 citation statements)

References 42 publications

Supporting

Mentioning

144

Contrasting

Unclassified

Order By: Relevance

“…Notably, rtt109 −/− mutants were not hypersensitive to the antifungal drugs fluconazole or amphotericin B (Fig. 2 D and E), both of which affect cell membrane synthesis (21). These data reinforce the notion that pharmacological sensitivities of the rtt109 −/− mutant cells are specifically related to genome stability.…”

Section: Resultssupporting

confidence: 75%

“…albicans is an opportunistic pathogen that poses a considerable public health problem, with an estimated 40% mortality rate for systemic candidiasis (19,20). Antifungal drug resistance is a major clinical problem, and few drugs are available to battle Candida infections (21). H3K56 acetylation appears to be much less abundant in mammals than in yeasts (22)(23)(24), and close homologs of Rtt109 are not detected outside of the fungal kingdom (25,26).…”

mentioning

confidence: 99%

See 1 more Smart Citation

Histone acetyltransferase Rtt109 is required for Candida albicans pathogenesis

Rosa

Boyartchuk

Zhu

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

128

127

View full text Add to dashboard Cite

Candida albicans is a ubiquitous opportunistic pathogen that is the most prevalent cause of hospital-acquired fungal infections. In mammalian hosts, C. albicans is engulfed by phagocytes that attack the pathogen with DNA-damaging reactive oxygen species (ROS). Acetylation of histone H3 lysine 56 (H3K56) by the fungal-specific histone acetyltransferase Rtt109 is important for yeast model organisms to survive DNA damage and maintain genome integrity. To assess the importance of Rtt109 for C. albicans pathogenicity, we deleted the predicted homolog of Rtt109 in the clinical C. albicans isolate, SC5314. C. albicans rtt109 −/− mutant cells lack acetylated H3K56 (H3K56ac) and are hypersensitive to genotoxic agents. Additionally, rtt109 −/− mutant cells constitutively display increased H2A S129 phosphorylation and elevated DNA repair gene expression, consistent with endogenous DNA damage. Importantly, C. albicans rtt109 −/− cells are significantly less pathogenic in mice and more susceptible to killing by macrophages in vitro than are wild-type cells. Via pharmacological inhibition of the host NADPH oxidase enzyme, we show that the increased sensitivity of rtt109 −/− cells to macrophages depends on the host's ability to generate ROS, providing a mechanistic link between the drug sensitivity, gene expression, and pathogenesis phenotypes. We conclude that Rtt109 is particularly important for fungal pathogenicity, suggesting a unique target for therapeutic antifungal compounds.acetylation | chromatin | fungal pathogenesis | DNA damage resistance | macrophage

show abstract

Section: Resultssupporting

confidence: 75%

mentioning

confidence: 99%

Histone acetyltransferase Rtt109 is required for Candida albicans pathogenesis

Rosa

Boyartchuk

Zhu

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

128

127

View full text Add to dashboard Cite

show abstract

“…It is known that steroids can induce a PDR state in both Candida albicans and S. cerevisiae [15,16] and the Pdr5p and Snq2p proteins of S. cerevisiae are able to efflux steroid hormones. Thus, yeast PDR transporters, similar to human Mdr1p, could be involved in the total sterol homeostasis in yeast cells [17].…”

Section: Introductionmentioning

confidence: 99%

Putative role for ABC multidrug exporters in yeast quorum sensing

et al. 2009

View full text Add to dashboard Cite

a b s t r a c tPleiotropic drug resistance (PDR) transporters play essential roles in cell resistance to various toxic compounds in various organisms including bacteria, mammals and yeasts. A large group of PDR transporters have been described in yeasts so far, including those that are controlled by transcription factor Pdr1p. Here, we show that besides their role in removing extracellularly added toxic compounds, the Pdr5p and Snq2p transporters play important physiological roles and significantly influence the developmental phases and physiology of yeast populations growing in a liquid culture. They appear to be involved in population quorum sensing, which consequently influences transcription factor Pdr1p level via feedback regulation.

show abstract

“…3 The widespread use of topical and systemic antifungal agents as conventional treatment for oral candidosis has resulted in the development of resistance in C. albicans. 7 Although resistance of C. albicans to polyenes is rare, several mechanisms of azole resistance 8 have been reported, including changes in the cell wall or plasma membrane, which lead to impaired azole uptake; overexpression of or mutations in the target enzyme of azoles; and the efflux of drugs mediated by membrane transport proteins. 9 Resistance appears to increase proportionally with the extend of previous exposure to the antifungal drugs.…”

mentioning

confidence: 99%

Susceptibility of Candida albicans to photodynamic therapy in a murine model of oral candidosis

Mima

Pavarina

Dovigo

et al. 2010

Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, an

141

130

View full text Add to dashboard Cite

Objective. In vivo studies of antimicrobial PDT in animal models of oral candidosis are scarce and the association of porphyrin and LED light has not been evaluated for in vivo photoinactivation of Candida. In this study the effectiveness of photodynamic therapy (PDT) on the inactivation of Candida albicans in vivo was evaluated. Study design. Seventy-one 6-week-old female Swiss mice were immunosuppressed, provided tetracycline to their drinking water, then orally swabbed with a suspension of C. albicans (10 7 CFU/mL). Four days after oral inoculation, PDT was performed on the dorsum of the tongue after topical administration of Photogem at 400, 500, or 1000 mg/L and followed 30 minutes later by illumination with LED light (305 J/cm 2 ) at 455 or 630 nm (n ϭ 5 each). After swabbing to recover yeast from the tongue, the number of surviving yeast cells was determined (CFU/mL) and analyzed by ANOVA and Holm-Sidak tests (P Ͻ .05). Animals were humanely killed, and the tongues surgically removed and processed for histological evaluation of presence of yeast and inflammatory reaction. Results. PDT resulted in a significant reduction in C. albicans recovered from the tongue (P Ͻ .001) when compared with mice from the positive control group. There was no difference between the concentrations of Photogem and LED light wavelengths used. Histological evaluation of the tongue revealed that PDT causes no significant adverse effects to the local mucosa. Conclusion. PDT promoted significant reduction in the viability of C. albicans biofilm without harming the tongue tissue.

show abstract

Candida albicans drug resistance – another way to cope with stress

Cited by 197 publications

References 42 publications

Histone acetyltransferase Rtt109 is required for Candida albicans pathogenesis

Histone acetyltransferase Rtt109 is required for Candida albicans pathogenesis

Putative role for ABC multidrug exporters in yeast quorum sensing

Susceptibility of Candida albicans to photodynamic therapy in a murine model of oral candidosis

Contact Info

Product

Resources

About