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Candida albicans Strain Maintenance, Replacement, and Microvariation Demonstrated by Multilocus Sequence Typing

Aberdeen Fungal Group, Institute of Medical Sciences, Aberdeen AB25 2ZD, United Kingdom,¹ Department of Biology, University of Pisa, Pisa, Italy,² Department of Medical Microbiology, Royal Free and University College Medical School, Royal Free Hospital, London, United Kingdom,³ Department of Microbiology and Immunology, Australian Candidaemia Study, Women's and Children's Hospital, North Adelaide, SA, Australia,⁴ Peter Medawar Building for Pathogen Research and Department of Zoology, University of Oxford, Oxford, United Kingdom⁵

Received 4 May 2006/ Returned for modification 18 May 2006/ Accepted 24 July 2006

We typed 165 Candida albicans isolates from 44 different sources by multilocus sequence typing (MLST) and ABC typing of rRNA genes and determined their homozygosity or heterozygosity at the mating-type-like locus (MTL). The isolates represented pairs or larger sets from individual sources, which allowed the determination of strain diversity within patients. A comparison of replicate sequence data determined a reproducibility threshold for regarding isolates as MLST indistinguishable. For 36 isolate sets, MLST and ABC typing showed indistinguishable or highly related strain types among isolates from different sites or from the same site at different times from each patient. This observation included 11 sets with at least one isolate from a blood culture and a nonsterile site from the same patient. For one patient, strain replacement was evidenced in the form of two sets of isolates from different hospital admissions where the strain types within each set were nearly identical but where the two sets differed both by MLST and ABC typing. MLST therefore confirms the existing view of C. albicans strain carriage. Microvariation, evidenced as small differences between MLST types, resulted in most instances from a loss of heterozygosity at one or more of the sequenced loci. Among isolate sets that showed major strain type differences, some isolates could be excluded as likely examples of handling errors during storage. However, for a minority of isolates, intermittent differences in ABC type for tightly clustered MLST types and intermittent appearances of MTL homozygosity lead us to propose that some C. albicans isolates, or all isolates under yet-to-be-determined conditions, maintain a high level of genetic diversity by mechanisms such as recombination, gene conversion, or chromosomal ploidy change.

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