Colonizing populations of Candida albicans are clonal in origin but undergo microevolution through C1 fragment reorganization as demonstrated by DNA fingerprinting and C1 sequencing

Abstract

The genetic homogeneity of nine commensal and infecting populations of Candida albicans has been assessed by fingerprinting multiple isolates from each population by Southern blot hybridization first with the Ca3 probe and then with the 0.98-kb C1 fragment of the Ca3 probe. The isolates from each population were highly related, demonstrating the clonal origin of each population, but each population contained minor variants, demonstrating microevolution. Variation in each case was limited to bands of the Ca3 fingerprint pattern which hybridized with the 0.98-kb C1 fragment. The C1 fragment was therefore sequenced and demonstrated to contain an RPS repetitive element. The C1 fragment also contained part or all of a true end of the RPS element. These results, therefore, demonstrate that most colonizing C. albicans populations in nonimmunosuppressed patients are clonal, that microevolution can be detected in every colonizing population by C1 hybridization, and that C1 contains the repeat RPS element.

Molecular methods for strain typing of Candida albicans : a review

“…The complex Ca3 probe has been used in a large range of epidemiological studies involving significant numbers of strains and was found to be highly effective in assessing microevolution within clonal populations over time, due primarily to the hypervariability of genomic sequences homologous to the C1 fragment of the probe Anderson et al 1993;Schmid et al 1993;Schr€ oppel et al 1994;Lockhart et al 1995Lockhart et al , 1996. The C1 region contains the repetitive DNA sequence (RPS element), which is present at different locations in the C. albicans genome (Iwaguchi et al 1992;Lockhart et al 1995). The microevolutionary changes identified by Ca3 are due to the insertion and deletion of the fulllength RPS elements at specific sites dispersed throughout the genome and thus can be detected after hybridization of genomic DNA with the C1 fragment of Ca3 (Lockhart et al 1995;Pujol et al 1999).…”

“…The C1 region contains the repetitive DNA sequence (RPS element), which is present at different locations in the C. albicans genome (Iwaguchi et al 1992;Lockhart et al 1995). The microevolutionary changes identified by Ca3 are due to the insertion and deletion of the fulllength RPS elements at specific sites dispersed throughout the genome and thus can be detected after hybridization of genomic DNA with the C1 fragment of Ca3 (Lockhart et al 1995;Pujol et al 1999). Moreover, Ca3 hybridization has proven to be reproducible and amenable to computer-assisted analysis.…”

“…The standard genome of C. albicans is diploid and composed of eight pairs of chromosome homologs, ranging in size from about 3Á3 to 0Á95 Mb (Chibana et al 2000). Candida albicans has a predominantly clonal mode of reproduction (Pujol et al 1993;Lockhart et al 1995;Mata et al 2000). It was the first medically important pathogenic fungus for which the complete genome sequence was determined (Jones et al 2004).…”

“…This underlines the need for implementing appropriate control measures, which obviously requires a high knowledge of the biology and the epidemiology of Candida species including C. albicans, that are recognized to be particularly complex. Indeed, the same healthy individual can harbour the same strain at different body locations, or carry unrelated strains at the same or different body sites (Kam and Xu 2002), strains can replace each other in recurrent infections , undergo microevolution (minor changes in genotype over a relatively small number of cell generations) (Lockhart et al 1995;Shin et al 2004;Bougnoux et al 2006) and substrain shuffling (changes in subpopulations within individuals over time) (Lockhart et al 1995;Lott and Scarborough 2008), be transferred from one individual to another (Vazquez et al 1993;Schmid et al 1995;Ben Abdeljelil et al 2011), specific strains may predominate in particular geographical areas and some strains may be endemic in some hospitals and can undergo microevolution in the hospital setting (Pfaller et al 1998;Viviani et al 2006). This highlights the need for efficient methods for typing and delineation of strains.…”

A review of molecular techniques to type Candida glabrata isolates

“…10 They demonstrated that both Cg6 and Cg12 probes discriminate microevolution within sequential isolates of C. glabrata, 10 as observed in clonal population of C. albicans grown over many generations with Ca3 probes. 35,36 The probes also contain invariant sequences which facilitate normalisation in computerassisted analysis that can be used in large epidemiological studies. When analysing diverse geographical collection of 107 clinical isolates, Dodgson et al [11] demonstrated that Cg6 and Cg12, in contrast to RAPD and MLST, discriminate between all isolates in all groups and were the better methods when analysing microevolution or nosocomial transmission.…”