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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

Candida auris has a highly divergent genome. a, b, c, d Synonymous Codon Usage distribution of Candida auris isolate 6684 with respect to C. albicans (SC-5314 (a) and WO-1 (b)), C. lusitaniae ATCC 42720 and C. glabrata CBS 138. These plots were generated by correspondence analysis and depict the variability in the sum of synonymous codon usage and amino acid usage. These graphs depict the codon usage bias relating it to the evolution of pathogenic fungus. a, b, c, d Whole (or draft) genome dot plot alignment showing genomic synteny of Candida auris isolate 6684 with respect to other well known pathogenic Candida species. The y-axis is the largest scaffold of Candida auris 6684 and the x-axis is the largest chromosome (or scaffold) of the corresponding genome being compared
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Fig4: Candida auris has a highly divergent genome. a, b, c, d Synonymous Codon Usage distribution of Candida auris isolate 6684 with respect to C. albicans (SC-5314 (a) and WO-1 (b)), C. lusitaniae ATCC 42720 and C. glabrata CBS 138. These plots were generated by correspondence analysis and depict the variability in the sum of synonymous codon usage and amino acid usage. These graphs depict the codon usage bias relating it to the evolution of pathogenic fungus. a, b, c, d Whole (or draft) genome dot plot alignment showing genomic synteny of Candida auris isolate 6684 with respect to other well known pathogenic Candida species. The y-axis is the largest scaffold of Candida auris 6684 and the x-axis is the largest chromosome (or scaffold) of the corresponding genome being compared

Mentions: To gain deeper insights into the genome conservation and evolution of C. auris with other pathogenic Candida species, we performed whole genome alignment of sequencing reads against C. albicans SC-5314, C. glabrata CBS-138, C. lusitaniae ATCC 42720 and Saccharomyces cerevisiae S288c. More than 99.5 % of the C. auris 6684 reads did not align to the current whole (or draft) genome sequences of these four species mentioned above. This indicates that C. auris 6684 is highly divergent at the genome level. To further investigate we compared synonymous codon usage between C. auris 6684, C. albicans SC-5314, C. albicans WO-1, C. lusitaniae ATCC 42720 and C. glabrata CBS-138 (Fig. 4a - d). The codon usage in C. auris 6684 shows very less overlaps to codon usage in C. albicans (SC-5314 and WO-1) as shown in Fig. 4a and b. The synonymous codon usage appears to be significantly overlapping for C. auris 6684 and C. lusitaniae which correlates and supports the relatedness found in the results of phylogenetic analyses (Figs. 3a and 4c). In addition, the codon usage in C. auris 6684 also shows fair overlap with C. glabrata where there was no similarity found at the genomic scale between the two (Fig. 4d). The difference in codon usage can be to enhance optimal protein structure and function from the already prevailing behaviours in C. albicans. This observation suggests the codon usage bias; which is required for understanding the selective pressures involved in evolution of these fungal species. In the same light, the dot plots of whole (or draft) genome comparison of C. auris 6684 with respect to C. albicans (SC-5314 and WO-1) and C. glabrata CBS-138 showed no linearity at the genome scale (Fig. 4a and d) which supports the observations seen in synonymous codon usage plots. C. auris 6684 genome seemed to have linear genomic synteny with C. lusitaniae genome which was very evident with the blastp results (Fig. 5) as well as synonymous codon usage.Fig. 4


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)

Candida auris has a highly divergent genome. a, b, c, d Synonymous Codon Usage distribution of Candida auris isolate 6684 with respect to C. albicans (SC-5314 (a) and WO-1 (b)), C. lusitaniae ATCC 42720 and C. glabrata CBS 138. These plots were generated by correspondence analysis and depict the variability in the sum of synonymous codon usage and amino acid usage. These graphs depict the codon usage bias relating it to the evolution of pathogenic fungus. a, b, c, d Whole (or draft) genome dot plot alignment showing genomic synteny of Candida auris isolate 6684 with respect to other well known pathogenic Candida species. The y-axis is the largest scaffold of Candida auris 6684 and the x-axis is the largest chromosome (or scaffold) of the corresponding genome being compared
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

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

Fig4: Candida auris has a highly divergent genome. a, b, c, d Synonymous Codon Usage distribution of Candida auris isolate 6684 with respect to C. albicans (SC-5314 (a) and WO-1 (b)), C. lusitaniae ATCC 42720 and C. glabrata CBS 138. These plots were generated by correspondence analysis and depict the variability in the sum of synonymous codon usage and amino acid usage. These graphs depict the codon usage bias relating it to the evolution of pathogenic fungus. a, b, c, d Whole (or draft) genome dot plot alignment showing genomic synteny of Candida auris isolate 6684 with respect to other well known pathogenic Candida species. The y-axis is the largest scaffold of Candida auris 6684 and the x-axis is the largest chromosome (or scaffold) of the corresponding genome being compared
Mentions: To gain deeper insights into the genome conservation and evolution of C. auris with other pathogenic Candida species, we performed whole genome alignment of sequencing reads against C. albicans SC-5314, C. glabrata CBS-138, C. lusitaniae ATCC 42720 and Saccharomyces cerevisiae S288c. More than 99.5 % of the C. auris 6684 reads did not align to the current whole (or draft) genome sequences of these four species mentioned above. This indicates that C. auris 6684 is highly divergent at the genome level. To further investigate we compared synonymous codon usage between C. auris 6684, C. albicans SC-5314, C. albicans WO-1, C. lusitaniae ATCC 42720 and C. glabrata CBS-138 (Fig. 4a - d). The codon usage in C. auris 6684 shows very less overlaps to codon usage in C. albicans (SC-5314 and WO-1) as shown in Fig. 4a and b. The synonymous codon usage appears to be significantly overlapping for C. auris 6684 and C. lusitaniae which correlates and supports the relatedness found in the results of phylogenetic analyses (Figs. 3a and 4c). In addition, the codon usage in C. auris 6684 also shows fair overlap with C. glabrata where there was no similarity found at the genomic scale between the two (Fig. 4d). The difference in codon usage can be to enhance optimal protein structure and function from the already prevailing behaviours in C. albicans. This observation suggests the codon usage bias; which is required for understanding the selective pressures involved in evolution of these fungal species. In the same light, the dot plots of whole (or draft) genome comparison of C. auris 6684 with respect to C. albicans (SC-5314 and WO-1) and C. glabrata CBS-138 showed no linearity at the genome scale (Fig. 4a and d) which supports the observations seen in synonymous codon usage plots. C. auris 6684 genome seemed to have linear genomic synteny with C. lusitaniae genome which was very evident with the blastp results (Fig. 5) as well as synonymous codon usage.Fig. 4

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