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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

PCR based diagnostic method to differentiate between C. auris and C. haemulonii. a Primers based on C. auris 6684 MFα gene gives a specific amplicon at 400 bp. b Amplification was not seen in the case of C. haemulonii 8176. However, four clinical isolates identified to be C. haemulonii by Manipal Hospital, showed a band at 400 bp. c The PFGE profile of these four clinical isolates was similar to that of C. auris 6684
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Fig8: PCR based diagnostic method to differentiate between C. auris and C. haemulonii. a Primers based on C. auris 6684 MFα gene gives a specific amplicon at 400 bp. b Amplification was not seen in the case of C. haemulonii 8176. However, four clinical isolates identified to be C. haemulonii by Manipal Hospital, showed a band at 400 bp. c The PFGE profile of these four clinical isolates was similar to that of C. auris 6684

Mentions: The sequence of the gene coding mating factor α is unique to each Candida species and therefore we designed PCR primers specifically for MF α gene. This PCR was tested on C. haemulonii 8176 obtained from MTCC, IMTECH and C. auris 6684. As evident in Fig. 8a, C. auris 6684 gave an amplicon at 400 bp which was not seen for C. haemulonii. This test was further extrapolated to other clinical isolates reported to be C. haemulonii and many of them turned to be PCR positive for C. auris (Fig. 8b). The same isolates also showed a similar PFGE pattern (Fig. 8c), thereby confirming the fact that these were misdiagnosed as C. haemulonii.Fig. 8


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)

PCR based diagnostic method to differentiate between C. auris and C. haemulonii. a Primers based on C. auris 6684 MFα gene gives a specific amplicon at 400 bp. b Amplification was not seen in the case of C. haemulonii 8176. However, four clinical isolates identified to be C. haemulonii by Manipal Hospital, showed a band at 400 bp. c The PFGE profile of these four clinical isolates was similar to that of C. auris 6684
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

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

Fig8: PCR based diagnostic method to differentiate between C. auris and C. haemulonii. a Primers based on C. auris 6684 MFα gene gives a specific amplicon at 400 bp. b Amplification was not seen in the case of C. haemulonii 8176. However, four clinical isolates identified to be C. haemulonii by Manipal Hospital, showed a band at 400 bp. c The PFGE profile of these four clinical isolates was similar to that of C. auris 6684
Mentions: The sequence of the gene coding mating factor α is unique to each Candida species and therefore we designed PCR primers specifically for MF α gene. This PCR was tested on C. haemulonii 8176 obtained from MTCC, IMTECH and C. auris 6684. As evident in Fig. 8a, C. auris 6684 gave an amplicon at 400 bp which was not seen for C. haemulonii. This test was further extrapolated to other clinical isolates reported to be C. haemulonii and many of them turned to be PCR positive for C. auris (Fig. 8b). The same isolates also showed a similar PFGE pattern (Fig. 8c), thereby confirming the fact that these were misdiagnosed as C. haemulonii.Fig. 8

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