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Draft genome of a commonly misdiagnosed multidrug resistant pathogen Candida auris.

Chatterjee S, Alampalli SV, Nageshan RK, Chettiar ST, Joshi S, Tatu US - BMC Genomics (2015)

Bottom Line: More than 99.5 % of the C. auris genomic reads did not align to the current whole (or draft) genome sequences of Candida albicans, Candida lusitaniae, Candida glabrata and Saccharomyces cerevisiae; thereby indicating its divergence from the active Candida clade.Comparison with the well-studied species Candida albicans showed that it shares significant virulence attributes with other pathogenic Candida species such as oligopeptide transporters, mannosyl transfersases, secreted proteases and genes involved in biofilm formation.Owing to its diversity at the genomic scale; we expect the genome sequence to be a useful resource to map species specific differences that will help develop accurate diagnostic markers and better drug targets.

View Article: PubMed Central - PubMed

Affiliation: Department of Biochemistry, Indian Institute of Science, Bengaluru, Karnataka, India, 560012. sharanya@biochem.iisc.ernet.in.

ABSTRACT

Background: Candida auris is a multidrug resistant, emerging agent of fungemia in humans. Its actual global distribution remains obscure as the current commercial methods of clinical diagnosis misidentify it as C. haemulonii. Here we report the first draft genome of C. auris to explore the genomic basis of virulence and unique differences that could be employed for differential diagnosis.

Results: More than 99.5 % of the C. auris genomic reads did not align to the current whole (or draft) genome sequences of Candida albicans, Candida lusitaniae, Candida glabrata and Saccharomyces cerevisiae; thereby indicating its divergence from the active Candida clade. The genome spans around 12.49 Mb with 8527 predicted genes. Functional annotation revealed that among the sequenced Candida species, it is closest to the hemiascomycete species Clavispora lusitaniae. Comparison with the well-studied species Candida albicans showed that it shares significant virulence attributes with other pathogenic Candida species such as oligopeptide transporters, mannosyl transfersases, secreted proteases and genes involved in biofilm formation. We also identified a plethora of transporters belonging to the ABC and major facilitator superfamily along with known MDR transcription factors which explained its high tolerance to antifungal drugs.

Conclusions: Our study emphasizes an urgent need for accurate fungal screening methods such as PCR and electrophoretic karyotyping to ensure proper management of fungemia. Our work highlights the potential genetic mechanisms involved in virulence and pathogenicity of an important emerging human pathogen namely C. auris. Owing to its diversity at the genomic scale; we expect the genome sequence to be a useful resource to map species specific differences that will help develop accurate diagnostic markers and better drug targets.

No MeSH data available.


Related in: MedlinePlus

ITS phylogeny and electrophoretic karyotyping reveals that Ci 6684 belongs to C. auris clade. a Phylogenetic tree based on the partial sequence of 18 s rRNA, ITS1, 5.8 s rRNA complete sequence, ITS2 and 28 s rRNA partial sequences of species belonging to the C. haemulonii complex and related Candida species. Our isolate Ci 6684 is related to C. auris as it falls in the same clade. b Electrophoretic karyotyping shows 5 bands similar to those reported for C. auris by Oh J B et al., where they reported genotypic relatedness between C. haemulonii and closely related species. C. albicans (lane 1) shows four distinct bands. Corresponding C. auris lane (lane 2) shows five bands
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Fig2: ITS phylogeny and electrophoretic karyotyping reveals that Ci 6684 belongs to C. auris clade. a Phylogenetic tree based on the partial sequence of 18 s rRNA, ITS1, 5.8 s rRNA complete sequence, ITS2 and 28 s rRNA partial sequences of species belonging to the C. haemulonii complex and related Candida species. Our isolate Ci 6684 is related to C. auris as it falls in the same clade. b Electrophoretic karyotyping shows 5 bands similar to those reported for C. auris by Oh J B et al., where they reported genotypic relatedness between C. haemulonii and closely related species. C. albicans (lane 1) shows four distinct bands. Corresponding C. auris lane (lane 2) shows five bands

Mentions: Phylogenetic tree based on the partial sequence of 18 s rRNA, ITS1, 5.8 s rRNA complete sequence, ITS2 and 28 s rRNA partial sequence revealed that Ci 6684 belongs to Candida auris clade of Korean and Indian isolates with 99 % bootstrapped confidence (Fig. 2a). To further confirm its origin, we performed multiple sequence alignment with the Indian C. auris isolates and found complete conservation of rRNA and ITS sequences (Additional file 5). The same isolate was also able to grow at 40 °C and 42 °C as reported for C. auris but not for C. haemulonii [20]. Electrophoretic karyotyping by PFGE of Ci6684 yielded 5 bands and the pattern was similar to that reported previously for C. auris [26] (Fig. 2b). Because diagnostic laboratories rely only on automated systems like Vitek 2 or APIC20C which routinely identifies C. auris as C. haemulonii or C. famata, the actual occurrence of C. auris fungemia is under reported [25, 27, 28]. Our results emphasize the need to develop accurate species identification system based on molecular typing methods to ensure proper management of fungemia. Another recently developed method for identifying C. auris by MALDI-TOF has also been reported [29]. Henceforth Ci 6684 will be referred to C. auris 6684 in the remaining study.Fig. 2


Draft genome of a commonly misdiagnosed multidrug resistant pathogen Candida auris.

Chatterjee S, Alampalli SV, Nageshan RK, Chettiar ST, Joshi S, Tatu US - BMC Genomics (2015)

ITS phylogeny and electrophoretic karyotyping reveals that Ci 6684 belongs to C. auris clade. a Phylogenetic tree based on the partial sequence of 18 s rRNA, ITS1, 5.8 s rRNA complete sequence, ITS2 and 28 s rRNA partial sequences of species belonging to the C. haemulonii complex and related Candida species. Our isolate Ci 6684 is related to C. auris as it falls in the same clade. b Electrophoretic karyotyping shows 5 bands similar to those reported for C. auris by Oh J B et al., where they reported genotypic relatedness between C. haemulonii and closely related species. C. albicans (lane 1) shows four distinct bands. Corresponding C. auris lane (lane 2) shows five bands
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4562351&req=5

Fig2: ITS phylogeny and electrophoretic karyotyping reveals that Ci 6684 belongs to C. auris clade. a Phylogenetic tree based on the partial sequence of 18 s rRNA, ITS1, 5.8 s rRNA complete sequence, ITS2 and 28 s rRNA partial sequences of species belonging to the C. haemulonii complex and related Candida species. Our isolate Ci 6684 is related to C. auris as it falls in the same clade. b Electrophoretic karyotyping shows 5 bands similar to those reported for C. auris by Oh J B et al., where they reported genotypic relatedness between C. haemulonii and closely related species. C. albicans (lane 1) shows four distinct bands. Corresponding C. auris lane (lane 2) shows five bands
Mentions: Phylogenetic tree based on the partial sequence of 18 s rRNA, ITS1, 5.8 s rRNA complete sequence, ITS2 and 28 s rRNA partial sequence revealed that Ci 6684 belongs to Candida auris clade of Korean and Indian isolates with 99 % bootstrapped confidence (Fig. 2a). To further confirm its origin, we performed multiple sequence alignment with the Indian C. auris isolates and found complete conservation of rRNA and ITS sequences (Additional file 5). The same isolate was also able to grow at 40 °C and 42 °C as reported for C. auris but not for C. haemulonii [20]. Electrophoretic karyotyping by PFGE of Ci6684 yielded 5 bands and the pattern was similar to that reported previously for C. auris [26] (Fig. 2b). Because diagnostic laboratories rely only on automated systems like Vitek 2 or APIC20C which routinely identifies C. auris as C. haemulonii or C. famata, the actual occurrence of C. auris fungemia is under reported [25, 27, 28]. Our results emphasize the need to develop accurate species identification system based on molecular typing methods to ensure proper management of fungemia. Another recently developed method for identifying C. auris by MALDI-TOF has also been reported [29]. Henceforth Ci 6684 will be referred to C. auris 6684 in the remaining study.Fig. 2

Bottom Line: More than 99.5 % of the C. auris genomic reads did not align to the current whole (or draft) genome sequences of Candida albicans, Candida lusitaniae, Candida glabrata and Saccharomyces cerevisiae; thereby indicating its divergence from the active Candida clade.Comparison with the well-studied species Candida albicans showed that it shares significant virulence attributes with other pathogenic Candida species such as oligopeptide transporters, mannosyl transfersases, secreted proteases and genes involved in biofilm formation.Owing to its diversity at the genomic scale; we expect the genome sequence to be a useful resource to map species specific differences that will help develop accurate diagnostic markers and better drug targets.

View Article: PubMed Central - PubMed

Affiliation: Department of Biochemistry, Indian Institute of Science, Bengaluru, Karnataka, India, 560012. sharanya@biochem.iisc.ernet.in.

ABSTRACT

Background: Candida auris is a multidrug resistant, emerging agent of fungemia in humans. Its actual global distribution remains obscure as the current commercial methods of clinical diagnosis misidentify it as C. haemulonii. Here we report the first draft genome of C. auris to explore the genomic basis of virulence and unique differences that could be employed for differential diagnosis.

Results: More than 99.5 % of the C. auris genomic reads did not align to the current whole (or draft) genome sequences of Candida albicans, Candida lusitaniae, Candida glabrata and Saccharomyces cerevisiae; thereby indicating its divergence from the active Candida clade. The genome spans around 12.49 Mb with 8527 predicted genes. Functional annotation revealed that among the sequenced Candida species, it is closest to the hemiascomycete species Clavispora lusitaniae. Comparison with the well-studied species Candida albicans showed that it shares significant virulence attributes with other pathogenic Candida species such as oligopeptide transporters, mannosyl transfersases, secreted proteases and genes involved in biofilm formation. We also identified a plethora of transporters belonging to the ABC and major facilitator superfamily along with known MDR transcription factors which explained its high tolerance to antifungal drugs.

Conclusions: Our study emphasizes an urgent need for accurate fungal screening methods such as PCR and electrophoretic karyotyping to ensure proper management of fungemia. Our work highlights the potential genetic mechanisms involved in virulence and pathogenicity of an important emerging human pathogen namely C. auris. Owing to its diversity at the genomic scale; we expect the genome sequence to be a useful resource to map species specific differences that will help develop accurate diagnostic markers and better drug targets.

No MeSH data available.


Related in: MedlinePlus