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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

In vitro antifungal susceptibility testing of clinical isolates of Candida: All the isolates were identified as C. haemulonii by Vitek2. Susceptibility testing was done by broth microdilution method at 37 °C for 48 h as mentioned in materials and methods. a Comparison of MIC50 values of all isolates for Fcz indicates all clinical isolates have MIC range of 32–64 μg/ml. b Comparison of MIC50 values of all isolates for AmB shows that all clinical isolates are resistant to AmB. Candida isolate Ci 6684 has the highest MIC50 value of > = 16 μg/ml
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Fig1: In vitro antifungal susceptibility testing of clinical isolates of Candida: All the isolates were identified as C. haemulonii by Vitek2. Susceptibility testing was done by broth microdilution method at 37 °C for 48 h as mentioned in materials and methods. a Comparison of MIC50 values of all isolates for Fcz indicates all clinical isolates have MIC range of 32–64 μg/ml. b Comparison of MIC50 values of all isolates for AmB shows that all clinical isolates are resistant to AmB. Candida isolate Ci 6684 has the highest MIC50 value of > = 16 μg/ml

Mentions: With the background of the growing incidences of candidiasis we have determined the hierarchy of the causative Candida species from clinical cases of invasive non-albicans candidiasis. In collaboration with Manipal Hospital, Bengaluru we have screened clinical samples from invasive cases of Candidiasis (Additional file 2: Table S1). Identification of the isolates was done by Vitek2 (bioMerieux, Marcy, I’Etoile, France) performed at Manipal Hospital. We saw a significant increase in the frequency of Candidiasis from 2012 to 2014 and we also found that non albicans Candida species are occupying the centre stage in such infections. Case reports from bloodstream infections revealed that in 2012, 24.3 % of infections were caused by C. albicans and C. tropicalis. However in 2014, 38.3 % of the cases were reported to be caused by C. haemulonii. Both C. albicans and C. tropicalis were susceptible to the commonly used antifungals AmB and Fcz (Table 1). However, all the clinical isolates identified as C. haemulonii showed increased tolerance to both Fcz and AmB. These isolates are referred as Candida isolates (Ci) henceforth. As shown in Fig. 1, the isolates had MIC50 value of >32 μg/mL and >7 μg/mL for Fcz and AmB (Fig. 1a,b) respectively. Since the patients were never administered AmB previously, it is difficult to comment that AmB resistance in these set of clinical isolates was inherent or acquired. However all these isolates were susceptible to caspofungin, the newer class of antifungal drugs- echinocandins (data not shown). The isolate Ci 6684 which showed resistance to both AmB and FcZ with highest MIC50 values was used for further analysis. The antifungal susceptibility profile of Ci 6684 is presented in Table 2.Fig. 1


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)

In vitro antifungal susceptibility testing of clinical isolates of Candida: All the isolates were identified as C. haemulonii by Vitek2. Susceptibility testing was done by broth microdilution method at 37 °C for 48 h as mentioned in materials and methods. a Comparison of MIC50 values of all isolates for Fcz indicates all clinical isolates have MIC range of 32–64 μg/ml. b Comparison of MIC50 values of all isolates for AmB shows that all clinical isolates are resistant to AmB. Candida isolate Ci 6684 has the highest MIC50 value of > = 16 μg/ml
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

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

Fig1: In vitro antifungal susceptibility testing of clinical isolates of Candida: All the isolates were identified as C. haemulonii by Vitek2. Susceptibility testing was done by broth microdilution method at 37 °C for 48 h as mentioned in materials and methods. a Comparison of MIC50 values of all isolates for Fcz indicates all clinical isolates have MIC range of 32–64 μg/ml. b Comparison of MIC50 values of all isolates for AmB shows that all clinical isolates are resistant to AmB. Candida isolate Ci 6684 has the highest MIC50 value of > = 16 μg/ml
Mentions: With the background of the growing incidences of candidiasis we have determined the hierarchy of the causative Candida species from clinical cases of invasive non-albicans candidiasis. In collaboration with Manipal Hospital, Bengaluru we have screened clinical samples from invasive cases of Candidiasis (Additional file 2: Table S1). Identification of the isolates was done by Vitek2 (bioMerieux, Marcy, I’Etoile, France) performed at Manipal Hospital. We saw a significant increase in the frequency of Candidiasis from 2012 to 2014 and we also found that non albicans Candida species are occupying the centre stage in such infections. Case reports from bloodstream infections revealed that in 2012, 24.3 % of infections were caused by C. albicans and C. tropicalis. However in 2014, 38.3 % of the cases were reported to be caused by C. haemulonii. Both C. albicans and C. tropicalis were susceptible to the commonly used antifungals AmB and Fcz (Table 1). However, all the clinical isolates identified as C. haemulonii showed increased tolerance to both Fcz and AmB. These isolates are referred as Candida isolates (Ci) henceforth. As shown in Fig. 1, the isolates had MIC50 value of >32 μg/mL and >7 μg/mL for Fcz and AmB (Fig. 1a,b) respectively. Since the patients were never administered AmB previously, it is difficult to comment that AmB resistance in these set of clinical isolates was inherent or acquired. However all these isolates were susceptible to caspofungin, the newer class of antifungal drugs- echinocandins (data not shown). The isolate Ci 6684 which showed resistance to both AmB and FcZ with highest MIC50 values was used for further analysis. The antifungal susceptibility profile of Ci 6684 is presented in Table 2.Fig. 1

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