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Antimicrobial Agents and Chemotherapy, April 1999, p. 836-845, Vol. 43, No. 4
0066-4804/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

High-Frequency, In Vitro Reversible Switching of Candida lusitaniae Clinical Isolates from Amphotericin B Susceptibility to Resistance

Stephanie A. Yoon,1 Jose A. Vazquez,*,1,2 Paul E. Steffan,2 Jack D. Sobel,1 and Robert A. Akins2

Department of Biochemistry & Molecular Biology,2 and Department of Medicine, Division of Infectious Diseases,1 Wayne State University School of Medicine, Detroit, Michigan

Received 4 May 1998/Returned for modification 28 July 1998/Accepted 24 January 1999

Recent studies have revealed an increase in the incidence of serious infections caused by non-albicans Candida species. Candida lusitaniae is of special interest because of its sporadic resistance to amphotericin B (AmB). The present in vitro study demonstrated that, unlike other Candida species, C. lusitaniae isolates frequently generated AmB-resistant lineages form previously susceptible colonies. Cells switching from a resistant colony to a susceptible phenotype were also detected after treatment with either UV light, heat shock, or exposure to whole blood, all of which increased the frequency of switching. In some C. lusitaniae lineages, after a cell switched to a resistant phenotype, the resistant phenotype was stable; in other lineages, colonies were composed primarily of AmB-susceptible cells. Although resistant and susceptible lineages were identical in many aspects, their cellular morphologies were dramatically different. Switching mechanisms that involve exposure to antifungals may have an impact on antifungal therapeutic strategies as well as on standardized susceptibility testing of clinical yeast specimens.


* Corresponding author. Present address: Division of Infectious Diseases, Harper Hospital, 3990 John R, 4 Yellow Center, Detroit, MI 48201. Phone: (313) 745-9649. Fax: (313) 993-0302. E-mail: jvazquez{at}oncgate.roc.wayne.edu.


Antimicrobial Agents and Chemotherapy, April 1999, p. 836-845, Vol. 43, No. 4
0066-4804/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.



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