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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

Evolutionary position of Candida auris isolate 6684 in the pathogenic fungal tree. a Phylogenetic tree based on orthologs of 95 conserved proteins from 11 pathogenic species under the phylum Ascomycota.b Amino acid substitution matrix by maximum likelihood estimation. c Tajima’s neutrality test indicates low level of polymorphism in the house keeping machinery wherein m = number of sequences, n = total number of sites, S = Number of segregating sites, ps = S/n, T = ps/a1, p = nucleotide diversity, and D is the Tajima test statistic. d Tajima’s relative rate test however indicates that these species have evolved at different rates. All evolutionary analyses were conducted in MEGA6
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Fig3: Evolutionary position of Candida auris isolate 6684 in the pathogenic fungal tree. a Phylogenetic tree based on orthologs of 95 conserved proteins from 11 pathogenic species under the phylum Ascomycota.b Amino acid substitution matrix by maximum likelihood estimation. c Tajima’s neutrality test indicates low level of polymorphism in the house keeping machinery wherein m = number of sequences, n = total number of sites, S = Number of segregating sites, ps = S/n, T = ps/a1, p = nucleotide diversity, and D is the Tajima test statistic. d Tajima’s relative rate test however indicates that these species have evolved at different rates. All evolutionary analyses were conducted in MEGA6

Mentions: In order to determine the evolutionary position of C. auris 6684 in the fungal genus tree, a concatenated phylogenetic tree was constructed based on orthologs of 95 conserved proteins (Additional file 2: Table S2) from 11 pathogenic species under the phylum Ascomycota (Fig. 3a). Our analysis shows bifurcation of C. albicans and C. auris 6684 in two distinct clades. However, we can see that C. auris 6684 and C. lusitaniae falls in the same clade, indicating convergence at the protein level. This is further confirmed by the amino acid substitution matrix of the house keeping machinery by maximum likelihood estimation wherein the number of amino acid substitutions per site between sequences is low (Fig. 3b). Tajima’s neutrality test indicates a positive D value which reflects low levels of polymorphism in the core housekeeping machinery of all these species including C. auris 6684 (Fig. 3c). Tajima’s relative rate test was performed to determine the heterogeneity of evolutionary rates between C. lusitaniae and C. auris 6684 with C. albicans used as an out group (Fig. 3d). The χ2 test statistic was 5.83 (P = 0.01580 with 1 degree of freedom). P-value was less than 0.05; hence hypothesis was rejected, thereby indicating different rates of evolution for these species.Fig. 3


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)

Evolutionary position of Candida auris isolate 6684 in the pathogenic fungal tree. a Phylogenetic tree based on orthologs of 95 conserved proteins from 11 pathogenic species under the phylum Ascomycota.b Amino acid substitution matrix by maximum likelihood estimation. c Tajima’s neutrality test indicates low level of polymorphism in the house keeping machinery wherein m = number of sequences, n = total number of sites, S = Number of segregating sites, ps = S/n, T = ps/a1, p = nucleotide diversity, and D is the Tajima test statistic. d Tajima’s relative rate test however indicates that these species have evolved at different rates. All evolutionary analyses were conducted in MEGA6
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

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

Fig3: Evolutionary position of Candida auris isolate 6684 in the pathogenic fungal tree. a Phylogenetic tree based on orthologs of 95 conserved proteins from 11 pathogenic species under the phylum Ascomycota.b Amino acid substitution matrix by maximum likelihood estimation. c Tajima’s neutrality test indicates low level of polymorphism in the house keeping machinery wherein m = number of sequences, n = total number of sites, S = Number of segregating sites, ps = S/n, T = ps/a1, p = nucleotide diversity, and D is the Tajima test statistic. d Tajima’s relative rate test however indicates that these species have evolved at different rates. All evolutionary analyses were conducted in MEGA6
Mentions: In order to determine the evolutionary position of C. auris 6684 in the fungal genus tree, a concatenated phylogenetic tree was constructed based on orthologs of 95 conserved proteins (Additional file 2: Table S2) from 11 pathogenic species under the phylum Ascomycota (Fig. 3a). Our analysis shows bifurcation of C. albicans and C. auris 6684 in two distinct clades. However, we can see that C. auris 6684 and C. lusitaniae falls in the same clade, indicating convergence at the protein level. This is further confirmed by the amino acid substitution matrix of the house keeping machinery by maximum likelihood estimation wherein the number of amino acid substitutions per site between sequences is low (Fig. 3b). Tajima’s neutrality test indicates a positive D value which reflects low levels of polymorphism in the core housekeeping machinery of all these species including C. auris 6684 (Fig. 3c). Tajima’s relative rate test was performed to determine the heterogeneity of evolutionary rates between C. lusitaniae and C. auris 6684 with C. albicans used as an out group (Fig. 3d). The χ2 test statistic was 5.83 (P = 0.01580 with 1 degree of freedom). P-value was less than 0.05; hence hypothesis was rejected, thereby indicating different rates of evolution for these species.Fig. 3

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