scholarly journals Development of Fluconazole Resistance inCandida albicansCausing Disseminated Infection in a Patient Undergoing Marrow Transplantation

1997 ◽  
Vol 25 (4) ◽  
pp. 908-910 ◽  
Author(s):  
Kieren A. Marr ◽  
Theodore C. White ◽  
Jo‐Anne H. van Burik ◽  
Raleigh A. Bowden
Keyword(s):  
Marrow Transplantation ◽  
Fluconazole Resistance ◽  
Disseminated Infection

scholarly journals Loss of Upc2p-InducibleERG3Transcription Is Sufficient To Confer Niche-Specific Azole Resistance without CompromisingCandida albicansPathogenicity

mBio ◽  
2018 ◽  
Vol 9 (3) ◽  
Author(s):  
Arturo Luna-Tapia ◽  
Hubertine M. E. Willems ◽  
Josie E. Parker ◽  
Hélène Tournu ◽  
Katherine S. Barker ◽  
...  
Keyword(s):  
Mouse Model ◽  
Stress Tolerance ◽  
Clinical Setting ◽  
Hyphal Growth ◽  
Antifungal Drugs ◽  
Azole Resistance ◽  
Fluconazole Resistance ◽  
Content Type ◽  
Disseminated Infection

ABSTRACTInactivation of sterol Δ5,6-desaturase (Erg3p) in the prevalent fungal pathogenCandida albicansis one of several mechanisms that can confer resistance to the azole antifungal drugs. However, loss of Erg3p activity is also associated with deficiencies in stress tolerance, invasive hyphal growth, and attenuated virulence in a mouse model of disseminated infection. This may explain why relatively fewerg3-deficient strains have been reported among azole-resistant clinical isolates. In this study, we examined the consequences of Erg3p inactivation uponC. albicanspathogenicity and azole susceptibility in mouse models of mucosal and disseminated infection. While aC. albicanserg3Δ/Δ mutant was unable to cause lethality in the disseminated model, it induced pathology in a mouse model of vaginal infection. Theerg3Δ/Δ mutant was also more resistant to fluconazole treatment than the wild type in both models of infection. Thus, complete loss of Erg3p activity confers azole resistance but also niche-specific virulence deficiencies. Serendipitously, we discovered that loss of azole-inducibleERG3transcription (rather than complete inactivation) is sufficient to conferin vitrofluconazole resistance, without compromisingC. albicansstress tolerance, hyphal growth, or pathogenicity in either mouse model. It is also sufficient to confer fluconazole resistance in the mouse vaginal model, but not in the disseminated model of infection, and thus confers niche-specific azole resistance without compromisingC. albicanspathogenicity at either site. Collectively, these results establish that modulating Erg3p expression or activity can have niche-specific consequences on bothC. albicanspathogenicity and azole resistance.IMPORTANCEWhile conferring resistance to the azole antifungalsin vitro, loss of sterol Δ5,6-desaturase (Erg3p) activity has also been shown to reduceC. albicanspathogenicity. Accordingly, it has been presumed that this mechanism may not be significant in the clinical setting. The results presented here challenge this assumption, revealing a more complex relationship between Erg3p activity, azole resistance,C. albicanspathogenicity, and the specific site of infection. Most importantly, we have shown that even modest changes inERG3transcription are sufficient to confer azole resistance without compromisingC. albicansfitness or pathogenicity. Given that previous efforts to assess the importance ofERG3as a determinant of clinical azole resistance have focused almost exclusively on detecting null mutants, its role may have been grossly underestimated. On the basis of our results, a more thorough investigation of the contribution of theERG3gene to azole resistance in the clinical setting is warranted.

Fatal Disseminated Infection by Scedosporium inflatum after Bone Marrow Transplantation

1993 ◽  
Vol 25 (3) ◽  
pp. 389-393 ◽  
Author(s):  
Ricardo Salesa ◽  
Angel Burgos ◽  
Ricardo Ondiviela ◽  
Carlos Richard ◽  
Guillermo Quindos ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Transplantation ◽  
Marrow Transplantation ◽  
Disseminated Infection

Infection in bone marrow transplantation

1983 ◽  
Vol 12 (3) ◽  
pp. 791-811 ◽  
Author(s):  
Joel D. Meyers ◽  
Kerry Atkinson
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Transplantation ◽  
Marrow Transplantation
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