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Antimicrob. Agents Chemother. doi:10.1128/AAC.00676-07
Copyright (c) 2007, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Paradoxical growth effect of caspofungin observed on biofilms and planktonic cells of five different Candida species

Division of Infectious Diseases, Universidade Federal de Sao Paulo, Sao Paulo, Brazil and Mycotic Diseases Branch, Centers for Disease Control and Prevention, Atlanta, GA

^* To whom correspondence should be addressed. Email: bskaggs{at}cdc.gov.

	Abstract

Paradoxical growth (PG) of Candida spp. biofilms in the presence of high caspofungin (CAS) concentrations was previously unknown. We sought to characterize PG at supra-MIC CAS concentrations among clinical Candida spp. isolates grown as biofilms in 96-well polystyrene microtiter plates. Planktonic and biofilm MICs of CAS were determined for 30 clinical Candida spp. isolates (4 C. albicans, 6 C. tropicalis, 7 C. parapsilosis, 8 C. orthopsilosis, 5 C. metapsilosis) and were defined as the lowest drug concentration that resulted in a prominent decrease in growth or a 50% reduction in metabolic activity, respectively. PG was defined as a resurgence of growth (>50% of that in the drug-free growth control well) at drug concentrations above the MIC. With the exception of C. tropicalis, all isolates displayed PG more frequently when grown as biofilms compared to planktonic cells. PG was undetectable among C. metapsilosis isolates in planktonic MIC tests but present in 100% of the isolates in biofilm MIC tests. The drug concentration and the number of drug dilutions supporting PG were higher for biofilms compared to planktonic cells. Microscopic changes in cell morphology were observed among both planktonic and biofilm PG cells. Specifically the accumulation of enlarged, globose cells was associated with PG and we hypothesize that CAS-induced changes in cell wall composition may be the explanation.

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