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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

Identification of mating gene MF α and mating loci in C. auris.a The amino acid sequence of the MF α gene. Regions encoding the mature α pheromone peptide is shown in blue color. Possible Kex2 cleavage sites are shown in red colour. Additional DA residues present in three of the peptides have been underlined. b Scaffold 18 shows conservation of non sex genes of MTL locus, however, MF α gene is present in a different scaffold
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Fig7: Identification of mating gene MF α and mating loci in C. auris.a The amino acid sequence of the MF α gene. Regions encoding the mature α pheromone peptide is shown in blue color. Possible Kex2 cleavage sites are shown in red colour. Additional DA residues present in three of the peptides have been underlined. b Scaffold 18 shows conservation of non sex genes of MTL locus, however, MF α gene is present in a different scaffold

Mentions: To understand the mode of reproduction in C auris, we analysed the MAT loci (MTL) in the genome assembly. Our search led to the identification of a putative gene sequence in C. auris 6684 genome with similarities to α mating pheromone of Naumovozyma castellii CBS 4309. The gene sequence consists of a 654-bp ORF that encodes for five putative α pheromone peptide repeats separated by KEX2 proteinase cleavage sites. Two of the five α-peptides are identical in sequence; the remaining three contains additional DA residues (Fig. 7). We also found a homologue of KEX2 in the genome. However, the genes in the vicinity of MF-α were all annotated as hypothetical (Additional file 2: Table S4). Interestingly, the three non-sex genes (NSGs) of the MTL locus namely, the essential phosphatidyl inositol kinase gene (PIK), the essential poly (A) polymerase gene (PAP), and the nonessential oxysterol binding protein gene (OBP) were present in a different scaffold (Fig. 7). In C. albicans, these genes have been implicated in biofilm impermeabilty and fluconazole resistance [50]. Thus MAT α gene is located in a different locus. In C. auris 6684, ERG11 is also located on the same scaffold as MTL non sex genes and in C. albicans, the loss of heterozygosity at the MTL locus has been correlated to azole resistance [51]. However we could not find MATa gene in the genome. Thorough experimentation needs to be done to establish its sexuality.Fig. 7


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)

Identification of mating gene MF α and mating loci in C. auris.a The amino acid sequence of the MF α gene. Regions encoding the mature α pheromone peptide is shown in blue color. Possible Kex2 cleavage sites are shown in red colour. Additional DA residues present in three of the peptides have been underlined. b Scaffold 18 shows conservation of non sex genes of MTL locus, however, MF α gene is present in a different scaffold
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

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

Fig7: Identification of mating gene MF α and mating loci in C. auris.a The amino acid sequence of the MF α gene. Regions encoding the mature α pheromone peptide is shown in blue color. Possible Kex2 cleavage sites are shown in red colour. Additional DA residues present in three of the peptides have been underlined. b Scaffold 18 shows conservation of non sex genes of MTL locus, however, MF α gene is present in a different scaffold
Mentions: To understand the mode of reproduction in C auris, we analysed the MAT loci (MTL) in the genome assembly. Our search led to the identification of a putative gene sequence in C. auris 6684 genome with similarities to α mating pheromone of Naumovozyma castellii CBS 4309. The gene sequence consists of a 654-bp ORF that encodes for five putative α pheromone peptide repeats separated by KEX2 proteinase cleavage sites. Two of the five α-peptides are identical in sequence; the remaining three contains additional DA residues (Fig. 7). We also found a homologue of KEX2 in the genome. However, the genes in the vicinity of MF-α were all annotated as hypothetical (Additional file 2: Table S4). Interestingly, the three non-sex genes (NSGs) of the MTL locus namely, the essential phosphatidyl inositol kinase gene (PIK), the essential poly (A) polymerase gene (PAP), and the nonessential oxysterol binding protein gene (OBP) were present in a different scaffold (Fig. 7). In C. albicans, these genes have been implicated in biofilm impermeabilty and fluconazole resistance [50]. Thus MAT α gene is located in a different locus. In C. auris 6684, ERG11 is also located on the same scaffold as MTL non sex genes and in C. albicans, the loss of heterozygosity at the MTL locus has been correlated to azole resistance [51]. However we could not find MATa gene in the genome. Thorough experimentation needs to be done to establish its sexuality.Fig. 7

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