Displaying publications 1 - 20 of 26 in total

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  1. Yew SM, Chan CL, Ngeow YF, Toh YF, Na SL, Lee KW, et al.
    Sci Rep, 2016 05 31;6:27008.
    PMID: 27243961 DOI: 10.1038/srep27008
    Cladosporium sphaerospermum, a dematiaceous saprophytic fungus commonly found in diverse environments, has been reported to cause allergy and other occasional diseases in humans. However, its basic biology and genetic information are largely unexplored. A clinical isolate C. sphaerospermum genome, UM 843, was re-sequenced and combined with previously generated sequences to form a model 26.89 Mb genome containing 9,652 predicted genes. Functional annotation on predicted genes suggests the ability of this fungus to degrade carbohydrate and protein complexes. Several putative peptidases responsible for lung tissue hydrolysis were identified. These genes shared high similarity with the Aspergillus peptidases. The UM 843 genome encodes a wide array of proteins involved in the biosynthesis of melanin, siderophores, cladosins and survival in high salinity environment. In addition, a total of 28 genes were predicted to be associated with allergy. Orthologous gene analysis together with 22 other Dothideomycetes showed genes uniquely present in UM 843 that encode four class 1 hydrophobins which may be allergens specific to Cladosporium. The mRNA of these hydrophobins were detected by RT-PCR. The genomic analysis of UM 843 contributes to the understanding of the biology and allergenicity of this widely-prevalent species.
  2. Yew SM, Chan CL, Lee KW, Na SL, Tan R, Hoh CC, et al.
    PLoS One, 2014;9(8):e104352.
    PMID: 25098697 DOI: 10.1371/journal.pone.0104352
    Dematiaceous fungi (black fungi) are a heterogeneous group of fungi present in diverse environments worldwide. Many species in this group are known to cause allergic reactions and potentially fatal diseases in humans and animals, especially in tropical and subtropical climates. This study represents the first survey of dematiaceous fungi in Malaysia and provides observations on their diversity as well as in vitro response to antifungal drugs. Seventy-five strains isolated from various clinical specimens were identified by morphology as well as an internal transcribed spacer (ITS)-based phylogenetic analysis. The combined molecular and conventional approach enabled the identification of three classes of the Ascomycota phylum and 16 genera, the most common being Cladosporium, Cochliobolus and Neoscytalidium. Several of the species identified have not been associated before with human infections. Among 8 antifungal agents tested, the azoles posaconazole (96%), voriconazole (90.7%), ketoconazole (86.7%) and itraconazole (85.3%) showed in vitro activity (MIC ≤ 1 µg/mL) to the largest number of strains, followed by anidulafungin (89.3%), caspofungin (74.7%) and amphotericin B (70.7%). Fluconazole appeared to be the least effective with only 10.7% of isolates showing in vitro susceptibility. Overall, almost half (45.3%) of the isolates showed reduced susceptibility (MIC >1 µg/mL) to at least one antifungal agent, and three strains (one Pyrenochaeta unguis-hominis and two Nigrospora oryzae) showed potential multidrug resistance.
  3. Yew SM, Chan CL, Soo-Hoo TS, Na SL, Ong SS, Hassan H, et al.
    Genome Announc, 2013;1(3).
    PMID: 23723391 DOI: 10.1128/genomeA.00158-13
    Pyrenochaeta, classified under the order Pleosporales, is known to cause diseases in plants and humans. Here, we report a draft genome sequence of a Pyrenochaeta sp. isolated from a skin scraping, with an estimated genome size of 39.4 Mb. Genes associated with the synthesis of proteases, toxins, plant cell wall degradation, and multidrug resistance were found.
  4. Yew SM, Chan CL, Kuan CS, Toh YF, Ngeow YF, Na SL, et al.
    BMC Genomics, 2016 Feb 03;17:91.
    PMID: 26842951 DOI: 10.1186/s12864-016-2409-8
    Ochroconis mirabilis, a recently introduced water-borne dematiaceous fungus, is occasionally isolated from human skin lesions and nails. We identified an isolate of O. mirabilis from a skin scraping with morphological and molecular studies. Its genome was then sequenced and analysed for genetic features related to classification and biological characteristics.
  5. Toh YF, Yew SM, Chan CL, Na SL, Lee KW, Hoh CC, et al.
    PLoS One, 2016;11(9):e0162095.
    PMID: 27626635 DOI: 10.1371/journal.pone.0162095
    Pyrenochaeta unguis-hominis is a rare human pathogen that causes infection in human skin and nail. P. unguis-hominis has received little attention, and thus, the basic biology and pathogenicity of this fungus is not fully understood. In this study, we performed in-depth analysis of the P. unguis-hominis UM 256 genome that was isolated from the skin scraping of a dermatitis patient. The isolate was identified to species level using a comprehensive multilocus phylogenetic analysis of the genus Pyrenochaeta. The assembled UM 256 genome has a size of 35.5 Mb and encodes 12,545 putative genes, and 0.34% of the assembled genome is predicted transposable elements. Its genomic features propose that the fungus is a heterothallic fungus that encodes a wide array of plant cell wall degrading enzymes, peptidases, and secondary metabolite biosynthetic enzymes. Antifungal drug resistance genes including MDR, CDR, and ERG11/CYP51 were identified in P. unguis-hominis UM 256, which may confer resistance to this fungus. The genome analysis of P. unguis-hominis provides an insight into molecular and genetic basis of the fungal lifestyles, understanding the unrevealed biology of antifungal resistance in this fungus.
  6. Tan KK, Tan YC, Chang LY, Lee KW, Nore SS, Yee WY, et al.
    BMC Genomics, 2015;16:93.
    PMID: 25888205 DOI: 10.1186/s12864-015-1294-x
    Brucellosis is an important zoonotic disease that affects both humans and animals. We sequenced the full genome and characterised the genetic diversity of two Brucella melitensis isolates from Malaysia and the Philippines. In addition, we performed a comparative whole-genome single nucleotide polymorphism (SNP) analysis of B. melitensis strains collected from around the world, to investigate the potential origin and the history of the global spread of B. melitensis.
  7. Tan KK, Tan YC, Chang LY, Lee KW, Nor'e SS, Yee WY, et al.
    J Infect Dev Ctries, 2017 Jun 01;11(5):420-425.
    PMID: 30943180 DOI: 10.3855/jidc.7598
    INTRODUCTION: Currently available tests have limitations for the identification of Brucella species and strains, and their genetic lineage. The genome sequence of the rpoB gene encoding the β-subunit of DNA-dependent RNA polymerase was investigated for its use in genotyping Brucella melitensis.

    METHODOLOGY: Complete rpoB gene sequences of globally distributed Brucella melitensis strains were analyzed. Single nucleotides polymorphisms (SNPs) of the rpoB gene sequences were identified and used to type Brucella melitensis strains.

    RESULTS: Six DNA polymorphisms were identified, of which two (nucleotides 3201 and 558) were novel. Analysis of the geographical distribution of the strains revealed a spatial clustering pattern with rpoB type 1 representing European and American strains, rpoB type 2 representing European, African, and Asian strains, rpoB type 3 representing Mediterranean strains, and rpoB type 4 representing African (C3201T) and European (C3201T/T558A) strains.

    CONCLUSIONS: We report the discovery of two novel SNPs of rpoB gene that can serve as useful markers for epidemiology and geographical tracking of B. melitensis.

  8. Ng KP, Yew SM, Chan CL, Soo-Hoo TS, Na SL, Hassan H, et al.
    Eukaryotic Cell, 2012 Jun;11(6):828.
    PMID: 22645233 DOI: 10.1128/EC.00133-12
    Pleosporales is the largest order in the fungal class Dothideomycetes. We report the 36,814,818-bp draft genome sequence and gene annotation of UM1110, a Pleosporales isolate associated with unclassified genera that is potentially a new fungal species. Analysis of the genome sequence led to the finding of genes associated with fungal adhesive proteins, secreted proteases, allergens, and pseudohyphal development.
  9. Ng KP, Ngeow YF, Yew SM, Hassan H, Soo-Hoo TS, Na SL, et al.
    Eukaryotic Cell, 2012 May;11(5):703-4.
    PMID: 22544898 DOI: 10.1128/EC.00074-12
    Daldinia eschscholzii is an invasive endophyte that is most commonly found in plant tissues rich in secondary metabolites. We report the draft genome sequence of D. eschscholzii isolated from blood culture. The draft genome is 35,494,957 bp in length, with 42,898,665 reads, 61,449 contigs, and a G+C content of 46.8%. The genome was found to contain a high abundance of genes associated with plant cell wall degradation enzymes, mycotoxin production, and antifungal drug resistance.
  10. Ng KP, Yew SM, Chan CL, Soo-Hoo TS, Na SL, Hassan H, et al.
    Eukaryotic Cell, 2012 May;11(5):705-6.
    PMID: 22544899 DOI: 10.1128/EC.00081-12
    Cladosporium sphaerospermum is one of the most widely distributed allergens causing serious problems in patients with respiratory tract disease. We report the 26,644,473-bp draft genome sequence and gene annotation of C. sphaerospermum UM843. Analysis of the genome sequence led to the finding of genes associated with C. sphaerospermum's melanin biosynthesis, allergens, and antifungal drug resistance.
  11. Ng KP, Yew SM, Chan CL, Tan R, Soo-Hoo TS, Na SL, et al.
    Genome Announc, 2013 Jan;1(1).
    PMID: 23409267 DOI: 10.1128/genomeA.00148-12
    Herpotrichiellaceae spp. are known to be opportunistic human pathogens. Here, we report the ~28.46-Mb draft genome of Herpotrichiellaceae sp. UM 238, isolated from human skin scraping. The UM 238 genome was found to contain many classes of protective genes that are responsible for fungal adaptation under adverse environmental conditions.
  12. Ng KP, Yew SM, Chan CL, Chong J, Tang SN, Soo-Hoo TS, et al.
    Genome Announc, 2013 Jan;1(1).
    PMID: 23405310 DOI: 10.1128/genomeA.00056-12
    The emergence of the global threat of extensively drug-resistant (XDR) Mycobacterium tuberculosis reveals weaknesses in tuberculosis management and diagnostic services. We report the draft genome sequence of the first extensively drug-resistant Mycobacterium tuberculosis strain isolated in Malaysia. The sequence was also compared against a reference strain to elucidate the polymorphism that is related to their extensive resistance.
  13. Looi HK, Toh YF, Yew SM, Na SL, Tan YC, Chong PS, et al.
    PeerJ, 2017;5:e2841.
    PMID: 28149676 DOI: 10.7717/peerj.2841
    Corynespora cassiicola is a common plant pathogen that causes leaf spot disease in a broad range of crop, and it heavily affect rubber trees in Malaysia (Hsueh, 2011; Nghia et al., 2008). The isolation of UM 591 from a patient's contact lens indicates the pathogenic potential of this dematiaceous fungus in human. However, the underlying factors that contribute to the opportunistic cross-infection have not been fully studied. We employed genome sequencing and gene homology annotations in attempt to identify these factors in UM 591 using data obtained from publicly available bioinformatics databases. The assembly size of UM 591 genome is 41.8 Mbp, and a total of 13,531 (≥99 bp) genes have been predicted. UM 591 is enriched with genes that encode for glycoside hydrolases, carbohydrate esterases, auxiliary activity enzymes and cell wall degrading enzymes. Virulent genes comprising of CAZymes, peptidases, and hypervirulence-associated cutinases were found to be present in the fungal genome. Comparative analysis result shows that UM 591 possesses higher number of carbohydrate esterases family 10 (CE10) CAZymes compared to other species of fungi in this study, and these enzymes hydrolyses wide range of carbohydrate and non-carbohydrate substrates. Putative melanin, siderophore, ent-kaurene, and lycopene biosynthesis gene clusters are predicted, and these gene clusters denote that UM 591 are capable of protecting itself from the UV and chemical stresses, allowing it to adapt to different environment. Putative sterigmatocystin, HC-toxin, cercosporin, and gliotoxin biosynthesis gene cluster are predicted. This finding have highlighted the necrotrophic and invasive nature of UM 591.
  14. Ling KH, Rajandream MA, Rivailler P, Ivens A, Yap SJ, Madeira AM, et al.
    Genome Res, 2007 Mar;17(3):311-9.
    PMID: 17284678
    Eimeria tenella is an intracellular protozoan parasite that infects the intestinal tracts of domestic fowl and causes coccidiosis, a serious and sometimes lethal enteritis. Eimeria falls in the same phylum (Apicomplexa) as several human and animal parasites such as Cryptosporidium, Toxoplasma, and the malaria parasite, Plasmodium. Here we report the sequencing and analysis of the first chromosome of E. tenella, a chromosome believed to carry loci associated with drug resistance and known to differ between virulent and attenuated strains of the parasite. The chromosome--which appears to be representative of the genome--is gene-dense and rich in simple-sequence repeats, many of which appear to give rise to repetitive amino acid tracts in the predicted proteins. Most striking is the segmentation of the chromosome into repeat-rich regions peppered with transposon-like elements and telomere-like repeats, alternating with repeat-free regions. Predicted genes differ in character between the two types of segment, and the repeat-rich regions appear to be associated with strain-to-strain variation.
  15. Kuan CS, Ismail R, Kwan Z, Yew SM, Yeo SK, Chan CL, et al.
    PLoS One, 2016;11(6):e0156119.
    PMID: 27280438 DOI: 10.1371/journal.pone.0156119
    A yeast-like organism was isolated from the skin scraping sample of a stasis dermatitis patient in the Mycology Unit Department of Medical Microbiology, University Malaya Medical Centre (UMMC), Kuala Lumpur, Malaysia. The isolate produced no pigment and was not identifiable using chromogenic agar and API 20C AUX. The fungus was identified as Metschnikowia sp. strain UM 1034, which is close to that of Metschnikowia drosophilae based on ITS- and D1/D2 domain-based phylogenetic analysis. However, the physiology of the strain was not associated to M. drosophilae. This pathogen exhibited low sensitivity to all tested azoles, echinocandins, 5-flucytosine and amphotericin B. This study provided insight into Metschnikowia sp. strain UM 1034 phenotype profiles using a Biolog phenotypic microarray (PM). The isolate utilized 373 nutrients of 760 nutrient sources and could adapt to a broad range of osmotic and pH environments. To our knowledge, this is the first report of the isolation of Metschnikowia non-pulcherrima sp. from skin scraping, revealing this rare yeast species as a potential human pathogen that may be misidentified as Candida sp. using conventional methods. Metschnikowia sp. strain UM 1034 can survive in flexible and diverse environments with a generalist lifestyle.
  16. Kuan CS, Yew SM, Toh YF, Chan CL, Lim SK, Lee KW, et al.
    PLoS One, 2015;10(12):e0145932.
    PMID: 26716988 DOI: 10.1371/journal.pone.0145932
    Peritonitis is the leading complication of peritoneal dialysis, which is primarily caused by bacteria rather than fungi. Peritonitis is responsible for approximately 18% of the infection-related mortality in peritoneal dialysis patients. In this paper, we report the isolation of a rare fungus, Quambalaria cyanescens, from the peritoneal fluid of a man after he switched from continuous ambulatory peritoneal dialysis to nocturnal intermittent peritoneal dialysis. Based on the morphological examination and multigene phylogeny, the clinical isolate was confirmed as Q. cyanescens. This pathogen exhibited low sensitivity to all tested echinocandins and 5-flucytosine. Interestingly, morphological characterization revealed that Q. cyanescens UM 1095 produced different pigments at low temperatures (25°C and 30°C) on various culture media. It is important to monitor the emergence of this rare fungus as a potential human pathogen in the tropics. This study provides insight into Q. cyanescens UM 1095 phenotype profiles using a Biolog phenotypic microarray (PM). Of the 760 nutrient sources tested, Q. cyanescens UM 1095 utilized 42 compounds, and the fungus can adapt to a broad range of osmotic and acidic environments. To our knowledge, this is the first report of the isolation of Q. cyanescens from peritoneal fluid, revealing this rare fungus as a potential human pathogen that may be misidentified using conventional methods. The detailed morphological, molecular and phenotypic characterization of Q. cyanescens UM 1095 provides the basis for future studies on its biology, lifestyle, and potential pathogenicity.
  17. Kuan CS, Yew SM, Chan CL, Toh YF, Lee KW, Cheong WH, et al.
    Database (Oxford), 2016;2016.
    PMID: 26980516 DOI: 10.1093/database/baw008
    Many species of dematiaceous fungi are associated with allergic reactions and potentially fatal diseases in human, especially in tropical climates. Over the past 10 years, we have isolated more than 400 dematiaceous fungi from various clinical samples. In this study, DemaDb, an integrated database was designed to support the integration and analysis of dematiaceous fungal genomes. A total of 92 072 putative genes and 6527 pathways that identified in eight dematiaceous fungi (Bipolaris papendorfii UM 226, Daldinia eschscholtzii UM 1400, D. eschscholtzii UM 1020, Pyrenochaeta unguis-hominis UM 256, Ochroconis mirabilis UM 578, Cladosporium sphaerospermum UM 843, Herpotrichiellaceae sp. UM 238 and Pleosporales sp. UM 1110) were deposited in DemaDb. DemaDb includes functional annotations for all predicted gene models in all genomes, such as Gene Ontology, EuKaryotic Orthologous Groups, Kyoto Encyclopedia of Genes and Genomes (KEGG), Pfam and InterProScan. All predicted protein models were further functionally annotated to Carbohydrate-Active enzymes, peptidases, secondary metabolites and virulence factors. DemaDb Genome Browser enables users to browse and visualize entire genomes with annotation data including gene prediction, structure, orientation and custom feature tracks. The Pathway Browser based on the KEGG pathway database allows users to look into molecular interaction and reaction networks for all KEGG annotated genes. The availability of downloadable files containing assembly, nucleic acid, as well as protein data allows the direct retrieval for further downstream works. DemaDb is a useful resource for fungal research community especially those involved in genome-scale analysis, functional genomics, genetics and disease studies of dematiaceous fungi. Database URL: http://fungaldb.um.edu.my.
  18. Kuan CS, Chan CL, Yew SM, Toh YF, Khoo JS, Chong J, et al.
    PLoS One, 2015;10(6):e0131694.
    PMID: 26110649 DOI: 10.1371/journal.pone.0131694
    The outbreak of extensively drug-resistant tuberculosis (XDR-TB) has become an increasing problem in many TB-burdened countries. The underlying drug resistance mechanisms, including the genetic variation favored by selective pressure in the resistant population, are partially understood. Recently, the first case of XDR-TB was reported in Malaysia. However, the detailed genotype family and mechanisms of the formation of multiple drugs resistance are unknown. We sequenced the whole genome of the UM 1072388579 strain with a 2-kb insert-size library and combined with that from previously sequenced 500-bp-insert paired-end reads to produce an improved sequence with maximal sequencing coverage across the genome. In silico spoligotyping and phylogenetic analyses demonstrated that UM 1072388579 strain belongs to an ancestral-like, non-Beijing clade of East Asia lineage. This is supported by the presence of a number of lineage-specific markers, including fadD28, embA, nuoD and pks7. Polymorphism analysis showed that the drug-susceptibility profile is correlated with the pattern of resistance mutations. Mutations in drug-efflux pumps and the cell wall biogenesis pathway such as mmpL, pks and fadD genes may play an important role in survival and adaptation of this strain to its surrounding environment. In this work, fifty-seven putative promoter SNPs were identified. Among them, we identified a novel SNP located at -4 T allele of TetR/acrR promoter as an informative marker to recognize strains of East Asian lineage. Our work indicates that the UM 1072388579 harbors both classical and uncommon SNPs that allow it to escape from inhibition by many antibiotics. This study provides a strong foundation to dissect the biology and underlying resistance mechanisms of the first reported XDR M. tuberculosis in Malaysia.
  19. Kuan CS, Cham CY, Singh G, Yew SM, Tan YC, Chong PS, et al.
    PLoS One, 2016;11(8):e0161008.
    PMID: 27570972 DOI: 10.1371/journal.pone.0161008
    Cladophialophora bantiana is a dematiaceous fungus with a predilection for causing central nervous system (CNS) infection manifesting as brain abscess in both immunocompetent and immunocompromised patients. In this paper, we report comprehensive genomic analyses of C. bantiana isolated from the brain abscess of an immunocompetent man, the first reported case in Malaysia and Southeast Asia. The identity of the fungus was determined using combined morphological analysis and multilocus phylogeny. The draft genome sequence of a neurotrophic fungus, C. bantiana UM 956 was generated using Illumina sequencing technology to dissect its genetic fundamental and basic biology. The assembled 37.1 Mb genome encodes 12,155 putative coding genes, of which, 1.01% are predicted transposable elements. Its genomic features support its saprophytic lifestyle, renowned for its versatility in decomposing hemicellulose and pectin components. The C. bantiana UM 956 was also found to carry some important putative genes that engaged in pathogenicity, iron uptake and homeostasis as well as adaptation to various stresses to enable the organism to survive in hostile microenvironment. This wealth of resource will further catalyse more downstream functional studies to provide better understanding on how this fungus can be a successful and persistent pathogen in human.
  20. Kuan CS, Ng KP, Yew SM, Umar Meleh H, Seow HF, How KN, et al.
    Braz J Microbiol, 2023 Sep;54(3):1351-1372.
    PMID: 37351789 DOI: 10.1007/s42770-023-01032-z
    Neoscytalidium dimidiatum and Bipolaris species are fungal plant pathogens that have been reported to cause human diseases. Recently, we have isolated numerous N. dimidiatum and Bipolaris species from the skin scrapings and nails of different patients. In this work, we have sequenced the genome of one strain of N. dimidiatum. The sequenced genome was compared to that of a previously reported Bipolaris papendorfii genome for a better understanding of their complex lifestyle and broad host-range pathogenicity. Both N. dimidiatum UM 880 (~ 43 Mb) and B. papendorfii UM 226 (~ 33 Mb) genomes include 11,015-12,320 putative coding DNA sequences, of which 0.51-2.49% are predicted transposable elements. Analysis of secondary metabolism gene clusters revealed several genes involved in melanin biosynthesis and iron uptake. The arsenal of CAZymes related to plants pathogenicity is comparable between the species, including genes involved in hemicellulose and pectin decomposition. Several important gene encoding keratinolytic peptidases were identified in N. dimidiatum and B. papendorfii, reflecting their potential pathogenic role in causing skin and nail infections. In this study, additional information on the metabolic features of these two species, such as nutritional profiling, pH tolerance, and osmotolerant, are revealed. The genomic characterization of N. dimidiatum and B. papendorfii provides the basis for the future functional studies to gain further insights as to what makes these fungi persist in plants and why they are pathogenic to humans.
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