Gain of function mutations in CgPDR1 of Candida glabrata not only mediate antifungal resistance but also enhance virulence

PLoS Pathogens

Volumn 5, Issue 1, 2009, Pages

  Ferrari, Sélène ^a   Ischer, Françoise ^a   Calabrese, David ^a,e   Posteraro, Brunella ^b   Sanguinetti, Maurizio ^b   Fadda, Giovanni ^b   Rohde, Bettina ^c   Bauser, Christopher ^c   Bader, Oliver ^d   Sanglard, Dominique ^a  

^a LAUSANNE UNIVERSITY HOSPITAL   (Switzerland)

^b CATHOLIC UNIVERSITY   (Italy)

^c GATC Biotech AG   (Germany)

^d UNIVERSITY MEDICAL CENTER GÖTTINGEN   (Germany)

^e Selexis SA   (Switzerland)

Author keywords

[No Author keywords available]

Indexed keywords

ABC TRANSPORTER; CIS ACTING ELEMENT; FLUCONAZOLE; FUNGAL PROTEIN; ITRACONAZOLE; KETOCONAZOLE; PROTEIN PDH1; PROTEIN PDR1; PYRROLE; TRANS ACTING FACTOR; TRANSCRIPTION FACTOR; UNCLASSIFIED DRUG;

ALLELE; AMINO ACID SUBSTITUTION; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ANTIFUNGAL RESISTANCE; ARTICLE; CANDIDA GLABRATA; CONTROLLED STUDY; FEMALE; FUNGAL STRAIN; FUNGAL VIRULENCE; GENE ACTIVITY; GENE EXPRESSION; GENE FUNCTION; GENE ISOLATION; GENE MUTATION; HUMAN; MOUSE; MYCOSIS; NONHUMAN; NUCLEOTIDE SEQUENCE; UPREGULATION; ANIMAL; BAGG ALBINO MOUSE; CANDIDIASIS; DRUG EFFECT; GENE EXPRESSION REGULATION; GENETICS; MICROBIOLOGY; MUTATION; PATHOGENICITY; VIRULENCE;

ANIMALIA; CANDIDA GLABRATA; MUS;

AMINO ACID SUBSTITUTION; ANIMALS; ATP-BINDING CASSETTE TRANSPORTERS; CANDIDA GLABRATA; CANDIDIASIS; DRUG RESISTANCE, FUNGAL; FEMALE; FLUCONAZOLE; GENE EXPRESSION REGULATION, FUNGAL; HUMANS; MICE; MICE, INBRED BALB C; MUTATION; TRANSCRIPTION FACTORS; VIRULENCE;

EID: 59249085257     PISSN: 15537366     EISSN: 15537374     Source Type: Journal    
DOI: 10.1371/journal.ppat.1000268     Document Type: Article

References (46)

1. Pappas PG, Rex JH, Lee J, Hamill RJ, Larsen RA, et al. (2003) A prospective observational study of candidemia: epidemiology, therapy, and influences on mortality in hospitalized adult and pediatric patients. Clin Infect Dis 37: 634-643.
2. Pfaller MA, Diekema DJ (2007) Epidemiology of invasive candidiasis: a persistent public health problem. Clin Microbiol Rev 20: 133-163.
3. Pfaller MA, Messer SA, Boyken L, Hollis RJ, Rice C, et al. (2004) In vitro activities of voriconazole, posaconazole, and fluconazole against 4,169 clinical isolates of Candida spp. and Cryptococcus neoformans collected during 2001 and 2002 in the ARTEMIS global antifungal surveillance program. Diagn Microbiol Infect Dis 48: 201-205.
4. Bennett JE, Izumikawa K, Marr KA (2004) Mechanism of increased fluconazole resistance in Candida glabrata during prophylaxis. Antimicrob Agents Chemother 48: 1773-1777.
5. Pfaller MA, Diekema DJ (2004) Twelve years of fluconazole in clinical practice: global trends in species distribution and fluconazole susceptibility of bloodstream isolates of Candida. Clin Microbiol Infect 10 Suppl 1: 11-23.
6. Pfaller MA, Messer SA, Boyken L, Tendolkar S, Hollis RJ, et al. (2003) Variation in susceptibility of bloodstream isolates of Candida glabrata to fluconazole according to patient age and geographic location. J Clin Microbiol 41: 2176-2179.
7. Sanglard D, Odds FC (2002) Resistance of Candida species to antifungal agents: molecular mechanisms and clinical consequences. Lancet Infect Dis 2: 73-85.
8. Miyazaki H, Miyazaki Y, Geber A, Parkinson T, Hitchcock C, et al. (1998) Fluconazole resistance associated with drug efflux and increased transcription of a drug transporter gene, PDH1, in Candida glabrata. Antimicrob Agents Chemother 42: 1695-1701.
9. Sanglard D, Ischer F, Bille J (2001) Role of ATP-binding-cassette transporter genes in high-frequency acquisition of resistance to azole antifungals in Candida glabrata. Antimicrob Agents Chemother 45: 1174-1183.
10. Sanglard D, Ischer F, Calabrese D, Majcherczyk PA, Bille J (1999) The ATP binding cassette transporter gene CgCDR1 from Candida glabrata is involved in the resistance of clinical isolates to azole antifungal agents. Antimicrob Agents Chemother 43: 2753-2765.
11. Vermitsky JP, Edlind TD (2004) Azole resistance in Candida glabrata: coordinate upregulation of multidrug transporters and evidence for a Pdr1-like transcription factor. Antimicrob Agents Chemother 48: 3773-3781.
12. Izumikawa K, Kakeya H, Tsai HF, Grimberg B, Bennett JE (2003) Function of Candida glabrata ABC transporter gene, PDH1. Yeast 20: 249-261.
13. Sanguinetti M, Posteraro B, Fiori B, Ranno S, Torelli R, et al. (2005) Mechanisms of azole resistance in clinical isolates of Candida glabrata collected during a hospital survey of antifungal resistance. Antimicrob Agents Chemother 49: 668-679.
14. Vermitsky JP, Earhart KD, Smith WL, Homayouni R, Edlind TD, et al. (2006) Pdr1 regulates multidrug resistance in Candida glabrata: gene disruption and genome-wide expression studies. Mol Microbiol 61: 704-722.
15. Tsai HF, Krol AA, Sarti KE, Bennett JE (2006) Candida glabrata PDR1, a transcriptional regulator of a pleiotropic drug resistance network, mediates azole resistance in clinical isolates and petite mutants. Antimicrob Agents Chemother 50: 1384-1392.
16. Thakur JK, Arthanari H, Yang F, Pan SJ, Fan X, et al. (2008) A nuclear receptor-like pathway regulating multidrug resistance in fungi. Nature 452: 604-609.
17. Torelli R, Posteraro B, Ferrari S, La Sorda M, Fadda G, et al. (2008) The ATP-binding cassette transporter-encoding gene CgSNQ2 is contributing to the CgPDR1-dependent azole resistance of Candida glabrata. Mol Microbiol 68: 186-201.
18. Bouchara JP, Zouhair R, Le Boudouil S, Renier G, Filmon R, et al. (2000) In-vivo selection of an azole-resistant petite mutant of Candida glabrata. J Med Microbiol 49: 977-984.
19. Kitada K, Yamaguchi E, Arisawa M (1996) Isolation of a Candida glabrata centromere and its use in construction of plasmid vectors. Gene 175: 105-108.
20. Barchiesi F, Spreghini E, Fothergill AW, Arzeni D, Greganti G, et al. (2005) Caspofungin in combination with amphotericin B against Candida glabrata. Antimicrob Agents Chemother 49: 2546-2549.
21. Kaur R, Ma B, Cormack BP (2007) A family of glycosylphosphatidylinositol- linked aspartyl proteases is required for virulence of Candida glabrata. Proc Natl Acad Sci U S A 104: 7628-7633.
22. MacCallum DM, Findon H, Kenny CC, Butler G, Haynes K, et al. (2006) Different consequences of ACE2 and SWI5 gene disruptions for virulence of pathogenic and nonpathogenic yeasts. Infect Immun 74: 5244-5248.
23. Delaveau T, Delahodde A, Carvajal E, Subik J, Jacq C (1994) PDR3, a new yeast regulatory gene, is homologous to PDR1 and controls the multidrug resistance phenomenon. Mol Gen Genet 244: 501-511.
24. Carvajal E, van den Hazel HB, Cybularz-Kolaczkowska A, Balzi E, Goffeau A (1997) Molecular and phenotypic characterization of yeast PDR1 mutants that show hyperactive transcription of various ABC multidrug transporter genes. Mol Gen Genet 256: 406-415.
25. MacPherson S, Larochelle M, Turcotte B (2006) A fungal family of transcriptional regulators: the zinc cluster proteins. Microbiol Mol Biol Rev 70: 583-604.
26. Delahodde A, Delaveau T, Jacq C (1995) Positive autoregulation of the yeast transcription factor Pdr3p, which is involved in control of drug resistance. Mol Cell Biol 15: 4043-4051.
27. Gygax SE, Vermitsky JP, Chadwick SG, Self MJ, Zimmerman JA, et al. (2008) Antifungal resistance of Candida glabrata vaginal isolates and development of a quantitative reverse transcription-PCR-based azole susceptibility assay. Antimicrob Agents Chemother 52: 3424-3426.
28. Anderson JB (2005) Evolution of antifungal-drug resistance: mechanisms and pathogen fitness. Nat Rev Microbiol 3: 547-556.
29. Andersson DI (2006) The biological cost of mutational antibiotic resistance: any practical conclusions? Curr Opin Microbiol 9: 461-465.
30. Warner DM, Folster JP, Shafer WM, Jerse AE (2007) Regulation of the MtrC-MtrD-MtrE efflux-pump system modulates the in vivo fitness of Neisseria gonorrhoeae. J Infect Dis 196: 1804-1812.
31. Gagneux S, Long CD, Small PM, Van T, Schoolnik GK, et al. (2006) The competitive cost of antibiotic resistance in Mycobacterium tuberculosis. Science 312: 1944-1946.
32. Graybill JR, Montalbo E, Kirkpatrick WR, Luther MF, Revankar SG, et al. (1998) Fluconazole versus Candida albicans: a complex relationship. Antimicrob Agents Chemother 42: 2938-2942.
33. Cowen LE, Kohn LM, Anderson JB (2001) Divergence in fitness and evolution of drug resistance in experimental populations of Candida albicans. J Bacteriol 183: 2971-2978.
34. Marr KA, Lyons CN, Rustad TR, Bowden RA, White TC (1998) Rapid, transient fluconazole resistance in Candida albicans is associated with increased mRNA levels of CDR. Antimicrob Agents Chemother 42: 2584-2589.
35. Marr KA, White TC, van Burik JA, Bowden RA (1997) Development of fluconazole resistance in Candida albicans causing disseminated infection in a patient undergoing marrow transplantation. Clin Infect Dis 25: 908-910.
36. Martins MD, Lozano-Chiu M, Rex JH (1998) Declining rates of oropharyngeal candidiasis and carriage of Candida albicans associated with trends toward reduced rates of carriage of fluconazole-resistant C. albicans in human immunodeficiency virus-infected patients. Clin Infect Dis 27: 1291-1294.
37. Arendrup M, Horn T, Frimodt-Moller N (2002) In vivo pathogenicity of eight medically relevant Candida species in an animal model. Infection 30: 286-291.
38. Brieland J, Essig D, Jackson C, Frank D, Loebenberg D, et al. (2001) Comparison of pathogenesis and host immune responses to Candida glabrata and Candida albicans in systemically infected immunocompetent mice. Infect Immun 69: 5046-5055.
39. Kamran M, Calcagno AM, Findon H, Bignell E, Jones MD, et al. (2004) Inactivation of transcription factor gene ACE2 in the fungal pathogen Candida glabrata results in hypervirulence. Eukaryot Cell 3: 546-552.
40. D'Souza CA, Alspaugh JA, Yue C, Harashima T, Cox GM, et al. (2001) Cyclic AMP-dependent protein kinase controls virulence of the fungal pathogen Cryptococcus neoformans. Mol Cell Biol 21: 3179-3191.
41. Ju JY, Polhamus C, Marr KA, Holland SM, Bennett JE (2002) Efficacies of fluconazole, caspofungin, and amphotericin B in Candida glabrata-infected p47phox-/- knockout mice. Antimicrob Agents Chemother 46: 1240-1245.
42. Marine M, Serena C, Fernandez-Torres B, Pastor FJ, Guarro J (2005) Activities of flucytosine, fluconazole, amphotericin B, and micafungin in a murine model of disseminated infection by Candida glabrata. Antimicrob Agents Chemother 49: 4757-4759.
43. Spreghini E, Maida CM, Tomassetti S, Orlando F, Giannini D, et al. (2008) Posaconazole against Candida glabrata isolates with various susceptibilities to fluconazole. Antimicrob Agents Chemother 52: 1929-1933.
44. Gumbo T, Drusano GL, Liu W, Ma L, Deziel MR, et al. (2006) Anidulafungin pharmacokinetics and microbial response in neutropenic mice with disseminated candidiasis. Antimicrob Agents Chemother 50: 3695-3700.
45. Goffeau A (2008) Drug resistance: the fight against fungi. Nature 452: 541-542.
46. Sanglard D, Ischer F, Calabrese D, Micheli M, Bille J (1998) Multiple resistance mechanisms to azole antifungals in yeast clinical isolates. Drug Resist Updat 1: 255-265.