Colony morphology switching of Candida lusitaniae and acquisition of multidrug resistance during treatment of a renal infection in a newborn: case report and review of the literature

Favel, Anne; Michel-Nguyen, A.; Peyron, F; Martin, Claude; Thomachot, Laurent; Datry, A.; Bouchara, Jean‐Philippe; Challier, S.; Noël, Thierry; Chastin, Christiane; Régli, P.

doi:10.1016/s0732-8893(03)00094-4

Cited by 62 publications

(65 citation statements)

References 54 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…It seems logical to conclude that different strains of C. lusitaniae may have different PS types. We and Yoon et al (27) noted differences in cell morphology/filamentation, whereas Favela et al (5) did not.…”

Section: Discussionmentioning

confidence: 47%

“…This has been reported for clinical strains of C. albicans from human immunodeficiency viruspositive individuals (26). In addition, data support a role for PS in AmB drug resistance in C. lusitaniae (5,27).…”

Section: Discussionmentioning

confidence: 85%

“…Other proposed mechanisms involve biosynthetic pathways, enzyme expression, and cell wall and cell membrane structures (6). There also are limited data suggesting that phenotypic switching (PS) may be responsible for changes in gene expression in C. lusitaniae, including those able to affect resistance to AmB and other antifungals (5,27).…”

mentioning

confidence: 99%

See 2 more Smart Citations

Phenotypic Switching in Candida lusitaniae on Copper Sulfate Indicator Agar: Association with Amphotericin B Resistance and Filamentation

2006

View full text Add to dashboard Cite

Candida lusitaniae is an opportunistic yeast pathogen that has the ability to develop resistance to amphotericin B (AmB). The mechanism(s) for this resistance is not well understood, although there are data supporting mutations in sterol pathways and other data supporting phenotypic switching (PS). The goal of this study was to determine whether C. lusitaniae has a PS system and to characterize any phenotypes, including any changes in AmB MICs. When 10 4 CFU of an AmB-resistant (MIC of 16 to 32 g/ml) clinical strain was plated on yeast-peptone-dextrose (YPD) agar with 1 mM CuSO 4 , three colony colors were observed: light brown (LB) Ͼ Ͼ dark brown (DB) > white (W), similar to the result for Candida glabrata. Switching did occur with high AmB resistance (MIC of 256 g/ml) being associated with W, whereas LB and DB colonies had MICs of 2 to 8 g/ml and 2 to 16 g/ml, respectively. Filamentation (pseudohyphae) was associated with DB colonies. All phenotypes occurred spontaneously with greater frequency (ϳ10 ؊2 to 10 ؊4 ) than spontaneous mutations, and all phenotypes were reversible, fulfilling the two PS criteria. High AmB MICs were always associated with W colonies but not with all W colonies. Detection of PS on YPD-CuSO 4 is also similar to that in Candida glabrata, and we hypothesize that this is due to similarities in metallothionein gene expression. Phenotypic switching represents a key strategy in C. lusitaniae that confers a selective advantage during environmental challenges, including the ability to switch to AmB resistance.

show abstract

Section: Discussionmentioning

confidence: 47%

Section: Discussionmentioning

confidence: 85%

See 1 more Smart Citation

Phenotypic Switching in Candida lusitaniae on Copper Sulfate Indicator Agar: Association with Amphotericin B Resistance and Filamentation

2006

View full text Add to dashboard Cite

show abstract

“…It is also an emerging pathogen which is characterized by its propensity to develop resistance to antifungal agents during treatment (16,24,31,32,47,52,58,60). The recent achievement of C. lusitaniae whole genome sequencing clearly reflects a growing interest of the scientific community in this opportunistic yeast.…”

mentioning

confidence: 99%

Differential Involvement of Histidine Kinase Receptors in Pseudohyphal Development, Stress Adaptation, and Drug Sensitivity of the Opportunistic Yeast Candida lusitaniae

et al. 2007

Self Cite

View full text Add to dashboard Cite

Fungal histidine kinase receptors (HKRs) sense and transduce many extracellular signals. We investigated the role of HKRs in morphogenetic transition, osmotolerance, oxidative stress response, and mating ability in the opportunistic yeast Candida lusitaniae. We isolated three genes, SLN1, NIK1, and CHK1, potentially encoding HKRs of classes VI, III, and X, respectively. These genes were disrupted by a transformation system based upon the "URA3 blaster" strategy. Functional analysis of disruptants was undertaken, except for the sln1 nik1 double mutant and the sln1 nik1 chk1 triple mutant, which are not viable in C. lusitaniae. The sln1 mutant revealed a high sensitivity to oxidative stress, whereas both the nik1 and chk1 mutants exhibited a more moderate sensitivity to peroxide. We also showed that the NIK1 gene was implicated in phenylpyrrole and dicarboximide compound susceptibility while HKRs seem not to be involved in resistance toward antifungals of clinical relevance. Concerning mating ability, all disruptants were still able to reproduce sexually in vitro in unilateral or bilateral crosses. The most important result of this study was that the sln1 mutant displayed a global defect of pseudohyphal differentiation, especially in high-osmolarity and oxidative-stress conditions. Thus, the SLN1 gene could be crucial for the C. lusitaniae yeast-to-pseudohypha morphogenetic transition. This implication is strengthened by a high level of SLN1 mRNAs revealed by semiquantitative reverse transcription-PCR when the yeast develops pseudohyphae. Our findings highlight a differential contribution of the three HKRs in osmotic and oxidant adaptation during the morphological transition in C. lusitaniae.Like bacteria, fungi and plants sense and transduce many extracellular signals through histidine kinase receptors (HKRs). In eukaryotic cells, these phosphorelay proteins often carry both a histidine kinase component and a response regulator domain. In response to an external signal, the histidine kinase component autophosphorylates a conserved histidine residue. The phosphate on this histidine is then transferred to a conserved aspartic acid in the response regulator domain. Such histidine-to-aspartate phosphotransfers initiate intracellular pathways mediated in particular by mitogen-activated protein (MAP) kinases (6, 40). In fungi, it is now accepted that HKRmediated transduction pathways are implicated in regulating diverse processes, including osmoregulation, morphogenesis, and virulence expression (62). Based on results from the fungal genome sequencing project (http//www.broad.mit.edu), a recent study provided a classification of several HKR genes identified in the Ascomycota and revealed that fungal HKRs fall into 11 classes (15). Most of these classes are encountered in each examined filamentous fungus, such as Neurospora crassa and Botryotinia fuckeliana, whereas Saccharomyces cerevisiae encodes only one HKR and the yeast species Schizosaccharomyces pombe and Candida albicans only three.The best-documented HKR-mediat...

show abstract

“…However, as these phenotypic characteristics may be variable, these methods may fail to discriminate between closely related species, leading to false or doubtful identifications, and may fail to detect new emergent pathogens (3,6,7). Candida lusitaniae, which is characterized by its propensity to develop resistance to amphotericin B during therapy, belongs to this important group of opportunistic pathogens (1,4). Interestingly, it is one of the opportunistic Candida species that have a known sexual cycle (4).…”

mentioning

confidence: 99%

Differentiation between Atypical Isolates of Candida lusitaniae and Candida pulcherrima by Determination of Mating Type

et al. 2005

Self Cite

View full text Add to dashboard Cite

We report on five clinical isolates routinely identified as Candida lusitaniae that the ID 32C system was unable to discriminate from the closely related species Candida pulcherrima. When additional tests did not allow accurate identification, the less usual mating type test identified all of them as Clavispora lusitaniae.Mating type testing appears to be a valuable tool for assessing the true incidence of this emerging non-albicans Candida species.The variety of non-albicans Candida species involved in human pathology, their rising contribution to invasive infections, and the unusual antifungal susceptibility profiles of some of these species make their identification to the species level essential for epidemiological investigations and for optimizing therapy and patient management (8). In clinical laboratories, routine identification is usually performed with commercial systems that have more or less broad databases and that often combine classical phenotypic tests, i.e., assimilation, biochemical, and morphology tests. However, as these phenotypic characteristics may be variable, these methods may fail to discriminate between closely related species, leading to false or doubtful identifications, and may fail to detect new emergent pathogens (3, 6, 7). Candida lusitaniae, which is characterized by its propensity to develop resistance to amphotericin B during therapy, belongs to this important group of opportunistic pathogens (1, 4). Interestingly, it is one of the opportunistic Candida species that have a known sexual cycle (4). Its teleomorph, Clavispora lusitaniae, is a heterothallic ascomycetous yeast from the Metschnikowiaceae family (11). A mating type test has thus been developed to unambiguously identify C. lusitaniae isolates (2).We report on five clinical isolates that the ID 32C system (bioMérieux, Marcy l'Etoile, France) suggested were either C. lusitaniae or Candida pulcherrima, another member of the Metschnikowiaceae family, which is a potential pathogen (4). These isolates were definitely identified as Clavispora lusitaniae through mating tests.The five clinical isolates were obtained from five patients hospitalized in four medical centers by partner clinical laboratories. They were recovered from stool (isolates 74 and 147), the upper respiratory tract (isolate 87), and blood (isolates 93 and 155). They were presumptively identified as C. lusitaniae by routine testing. Before they were added to our collection, their identities were checked with the ID 32C system. The test was performed in accordance with the manufacturer's instructions. Growth in each well was determined by visual reading after 48 h of incubation. Results were recorded as a 10-digit numerical profile (biocode), which was analyzed by the API Lab software (bioMérieux). Depending on the results, identification can be made to the species or genus level or can be considered unreliable. The results were given as an identification percentage (%id) that represents the relative proximity of the profile obtained for the taxon to those of ...

show abstract

Colony morphology switching of Candida lusitaniae and acquisition of multidrug resistance during treatment of a renal infection in a newborn: case report and review of the literature

Cited by 62 publications

References 54 publications

Phenotypic Switching in Candida lusitaniae on Copper Sulfate Indicator Agar: Association with Amphotericin B Resistance and Filamentation

Phenotypic Switching in Candida lusitaniae on Copper Sulfate Indicator Agar: Association with Amphotericin B Resistance and Filamentation

Differential Involvement of Histidine Kinase Receptors in Pseudohyphal Development, Stress Adaptation, and Drug Sensitivity of the Opportunistic Yeast Candida lusitaniae

Differentiation between Atypical Isolates of Candida lusitaniae and Candida pulcherrima by Determination of Mating Type

Contact Info

Product

Resources

About