Displaying publications 1 - 20 of 56 in total

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  1. Zheng W, Mutha NV, Heydari H, Dutta A, Siow CC, Jakubovics NS, et al.
    PeerJ, 2016;4:e1698.
    PMID: 27017950 DOI: 10.7717/peerj.1698
    Background. The gram-negative Neisseria is associated with two of the most potent human epidemic diseases: meningococcal meningitis and gonorrhoea. In both cases, disease is caused by bacteria colonizing human mucosal membrane surfaces. Overall, the genus shows great diversity and genetic variation mainly due to its ability to acquire and incorporate genetic material from a diverse range of sources through horizontal gene transfer. Although a number of databases exist for the Neisseria genomes, they are mostly focused on the pathogenic species. In this present study we present the freely available NeisseriaBase, a database dedicated to the genus Neisseria encompassing the complete and draft genomes of 15 pathogenic and commensal Neisseria species. Methods. The genomic data were retrieved from National Center for Biotechnology Information (NCBI) and annotated using the RAST server which were then stored into the MySQL database. The protein-coding genes were further analyzed to obtain information such as calculation of GC content (%), predicted hydrophobicity and molecular weight (Da) using in-house Perl scripts. The web application was developed following the secure four-tier web application architecture: (1) client workstation, (2) web server, (3) application server, and (4) database server. The web interface was constructed using PHP, JavaScript, jQuery, AJAX and CSS, utilizing the model-view-controller (MVC) framework. The in-house developed bioinformatics tools implemented in NeisseraBase were developed using Python, Perl, BioPerl and R languages. Results. Currently, NeisseriaBase houses 603,500 Coding Sequences (CDSs), 16,071 RNAs and 13,119 tRNA genes from 227 Neisseria genomes. The database is equipped with interactive web interfaces. Incorporation of the JBrowse genome browser in the database enables fast and smooth browsing of Neisseria genomes. NeisseriaBase includes the standard BLAST program to facilitate homology searching, and for Virulence Factor Database (VFDB) specific homology searches, the VFDB BLAST is also incorporated into the database. In addition, NeisseriaBase is equipped with in-house designed tools such as the Pairwise Genome Comparison tool (PGC) for comparative genomic analysis and the Pathogenomics Profiling Tool (PathoProT) for the comparative pathogenomics analysis of Neisseria strains. Discussion. This user-friendly database not only provides access to a host of genomic resources on Neisseria but also enables high-quality comparative genome analysis, which is crucial for the expanding scientific community interested in Neisseria research. This database is freely available at http://neisseria.um.edu.my.
  2. Zheng W, Tan TK, Paterson IC, Mutha NV, Siow CC, Tan SY, et al.
    PLoS One, 2016;11(5):e0151908.
    PMID: 27138013 DOI: 10.1371/journal.pone.0151908
    The oral streptococci are spherical Gram-positive bacteria categorized under the phylum Firmicutes which are among the most common causative agents of bacterial infective endocarditis (IE) and are also important agents in septicaemia in neutropenic patients. The Streptococcus mitis group is comprised of 13 species including some of the most common human oral colonizers such as S. mitis, S. oralis, S. sanguinis and S. gordonii as well as species such as S. tigurinus, S. oligofermentans and S. australis that have only recently been classified and are poorly understood at present. We present StreptoBase, which provides a specialized free resource focusing on the genomic analyses of oral species from the mitis group. It currently hosts 104 S. mitis group genomes including 27 novel mitis group strains that we sequenced using the high throughput Illumina HiSeq technology platform, and provides a comprehensive set of genome sequences for analyses, particularly comparative analyses and visualization of both cross-species and cross-strain characteristics of S. mitis group bacteria. StreptoBase incorporates sophisticated in-house designed bioinformatics web tools such as Pairwise Genome Comparison (PGC) tool and Pathogenomic Profiling Tool (PathoProT), which facilitate comparative pathogenomics analysis of Streptococcus strains. Examples are provided to demonstrate how StreptoBase can be employed to compare genome structure of different S. mitis group bacteria and putative virulence genes profile across multiple streptococcal strains. In conclusion, StreptoBase offers access to a range of streptococci genomic resources as well as analysis tools and will be an invaluable platform to accelerate research in streptococci. Database URL: http://streptococcus.um.edu.my.
  3. Zheng W, Tan MF, Old LA, Paterson IC, Jakubovics NS, Choo SW
    Sci Rep, 2017 06 07;7(1):2949.
    PMID: 28592797 DOI: 10.1038/s41598-017-02399-4
    Streptococcus gordonii and Streptococcus sanguinis are pioneer colonizers of dental plaque and important agents of bacterial infective endocarditis (IE). To gain a greater understanding of these two closely related species, we performed comparative analyses on 14 new S. gordonii and 5 S. sanguinis strains using various bioinformatics approaches. We revealed S. gordonii and S. sanguinis harbor open pan-genomes and share generally high sequence homology and number of core genes including virulence genes. However, we observed subtle differences in genomic islands and prophages between the species. Comparative pathogenomics analysis identified S. sanguinis strains have genes encoding IgA proteases, mitogenic factor deoxyribonucleases, nickel/cobalt uptake and cobalamin biosynthesis. On the contrary, genomic islands of S. gordonii strains contain additional copies of comCDE quorum-sensing system components involved in genetic competence. Two distinct polysaccharide locus architectures were identified, one of which was exclusively present in S. gordonii strains. The first evidence of genes encoding the CylA and CylB system by the α-haemolytic S. gordonii is presented. This study provides new insights into the genetic distinctions between S. gordonii and S. sanguinis, which yields understanding of tooth surfaces colonization and contributions to dental plaque formation, as well as their potential roles in the pathogenesis of IE.
  4. Wong YL, Choo SW, Tan JL, Ong CS, Ng KP, Ngeow YF
    J Bacteriol, 2012 Aug;194(16):4475.
    PMID: 22843600 DOI: 10.1128/JB.00916-12
    The whole-genome sequence of Mycobacterium bolletii M24, isolated from the bronchoalveolar lavage fluid of a Malaysian patient, is reported here. The circular chromosome of 5,507,730 bp helped to clarify the taxonomic position of this organism within the M. abscessus complex and revealed the presence of proteins potentially important for pathogenicity in a human host.
  5. Wee WY, Tan TK, Jakubovics NS, Choo SW
    PLoS One, 2016;11(3):e0152682.
    PMID: 27031249 DOI: 10.1371/journal.pone.0152682
    Mycobacterium brisbanense is a member of Mycobacterium fortuitum third biovariant complex, which includes rapidly growing Mycobacterium spp. that normally inhabit soil, dust and water, and can sometimes cause respiratory tract infections in humans. We present the first whole-genome analysis of M. brisbanense UM_WWY which was isolated from a 70-year-old Malaysian patient. Molecular phylogenetic analyses confirmed the identification of this strain as M. brisbanense and showed that it has an unusually large genome compared with related mycobacteria. The large genome size of M. brisbanense UM_WWY (~7.7Mbp) is consistent with further findings that this strain has a highly variable genome structure that contains many putative horizontally transferred genomic islands and prophage. Comparative analysis showed that M. brisbanense UM_WWY is the only Mycobacterium species that possesses a complete set of genes encoding enzymes involved in the urea cycle, suggesting that this soil bacterium is able to synthesize urea for use as plant fertilizers. It is likely that M. brisbanense UM_WWY is adapted to live in soil as its primary habitat since the genome contains many genes associated with nitrogen metabolism. Nevertheless, a large number of predicted virulence genes were identified in M. brisbanense UM_WWY that are mostly shared with well-studied mycobacterial pathogens such as Mycobacterium tuberculosis and Mycobacterium abscessus. These findings are consistent with the role of M. brisbanense as an opportunistic pathogen of humans. The whole-genome study of UM_WWY has provided the basis for future work of M. brisbanense.
  6. Wee WY, Dutta A, Jayaraj J, Choo SW
    PLoS One, 2019;14(4):e0214663.
    PMID: 30964891 DOI: 10.1371/journal.pone.0214663
    Mycobacterium cosmeticum is a nontuberculous Mycobacterium recovered from different water sources including household potable water and water collected at nail salon. Individual cases of this bacterium have been reported to be associated with gastrointestinal tract infections. Here we present the first whole-genome study and comparative analysis of two new clinically-derived Mycobacterium sp. UM_RHS (referred as UM_RHS after this) and Mycobacterium sp. UM_NYF (referred as UM_NYF after this) isolated from patients in Indonesia and Malaysia respectively to have a better understanding of the biological characteristic of these isolates. Both strains are likely Mycobacterium cosmeticum as supported by the evidence from molecular phylogenetic, comparative genomic and Average Nucleotide Identity (ANI) analyses. We found the presence of a considerably large number of putative virulence genes in the genomes of UM_RHS and UM_NYF. Interestingly, we also found a horizontally transferred genomic island carrying a putative dsz operon proposing that they may have potential to perform biodesulfization of dibenzothiophene (DBT) that may be effective in cost reduction and air pollution during fuel combustion. This comparative study may provide new insights into M. cosmeticum and serve as an important reference for future functional studies of this bacterial species.
  7. Wee WY, Dutta A, Choo SW
    PLoS One, 2017;12(3):e0172831.
    PMID: 28291784 DOI: 10.1371/journal.pone.0172831
    Mycobacteria a genus of Actinobacteria are widespread in nature ranging from soil-dwelling saprophytes to human and animal pathogens. The rate of growth has been a classifying factor for the Mycobacterium spp., dividing them into the rapid growers and the slow growers. Here we have performed a comparative genome study of mycobacterial species in order to get better understanding of their evolution, particularly to understand the distinction between the rapid and slow growers. Our study shows that the slow growers had generally gained and lost more genes compared to the rapid growers. The slow growers might haved eventually lost genes (LivFGMH operon, shaACDEFG genes and MspA porin) that could contribute to the slow growth rate of the slow growers. The genes gained and lost in mycobacteria had eventually helped these bacteria to adapt to different environments and have led to the evolution of the present day rapid and slow growers. Our results also show high number of Mycobacterium abscessus specific genes (811 genes) and some of them are associated with the known bacterial quorum sensing genes that might be important for Mycobacterium abscessus to adapt and survive in variety of unfavorable environments. Mycobacterium abscessus also does not contains genes involved in the bacterial defense system and together with the quorum sensing genes may have contributed to the high gene gain rate of Mycobacterium abscessus.
  8. Tian X, Teo WFA, Wee WY, Yang Y, Ahmed H, Jakubovics NS, et al.
    BMC Genomics, 2023 Dec 04;24(1):734.
    PMID: 38049764 DOI: 10.1186/s12864-023-09831-2
    BACKGROUND: Actinomyces strains are commonly found as part of the normal microflora on human tissue surfaces, including the oropharynx, gastrointestinal tract, and female genital tract. Understanding the diversity and characterization of Actinomyces species is crucial for human health, as they play an important role in dental plaque formation and biofilm-related infections. Two Actinomyces strains ATCC 49340 T and ATCC 51655 T have been utilized in various studies, but their accurate species classification and description remain unresolved.

    RESULTS: To investigate the genomic properties and taxonomic status of these strains, we employed both 16S rRNA Sanger sequencing and whole-genome sequencing using the Illumina HiSeq X Ten platform with PE151 (paired-end) sequencing. Our analyses revealed that the draft genome of Actinomyces acetigenes ATCC 49340 T was 3.27 Mbp with a 68.0% GC content, and Actinomyces stomatis ATCC 51655 T has a genome size of 3.08 Mbp with a 68.1% GC content. Multi-locus (atpA, rpoB, pgi, metG, gltA, gyrA, and core genome SNPs) sequence analysis supported the phylogenetic placement of strains ATCC 51655 T and ATCC 49340 T as independent lineages. Digital DNA-DNA hybridization (dDDH), average nucleotide identity (ANI), and average amino acid identity (AAI) analyses indicated that both strains represented novel Actinomyces species, with values below the threshold for species demarcation (70% dDDH, 95% ANI and AAI). Pangenome analysis identified 5,731 gene clusters with strains ATCC 49340 T and ATCC 51655 T possessing 1,515 and 1,518 unique gene clusters, respectively. Additionally, genomic islands (GIs) prediction uncovered 24 putative GIs in strain ATCC 49340 T and 16 in strain ATCC 51655 T, contributing to their genetic diversity and potential adaptive capabilities. Pathogenicity analysis highlighted the potential human pathogenicity risk associated with both strains, with several virulence-associated factors identified. CRISPR-Cas analysis exposed the presence of CRISPR and Cas genes in both strains, indicating these strains might evolve a robust defense mechanism against them.

    CONCLUSION: This study supports the classification of strains ATCC 49340 T and ATCC 51655 T as novel species within the Actinomyces, in which the name Actinomyces acetigenes sp. nov. (type strain ATCC 49340 T = VPI D163E-3 T = CCUG 34286 T = CCUG 35339 T) and Actinomyces stomatis sp. nov. (type strain ATCC 51655 T = PK606T = CCUG 33930 T) are proposed.

  9. Teo WF, Wee WY, Choo SW, Tan GY
    Mar Genomics, 2015 Apr;20:11-2.
    PMID: 25554669 DOI: 10.1016/j.margen.2014.12.006
    The bacterium strain SE31, a member of the genus Sciscionella, was isolated from intertidal sediments collected from Cape Rachado, Malaysia. The high quality draft genome sequence of Sciscionella strain SE31 with a genome size of approximately 7.4 Mbp is reported. Preliminary analysis revealed 46 putative gene clusters involved in the biosynthesis of secondary metabolites and 113 putative genes that are associated with bacterial virulence, disease and defense. Availability of the genome sequence of Sciscionella SE31 will contribute to a better understanding of the genus Sciscionella.
  10. Tay ST, Kho KL, Wee WY, Choo SW
    Acta Trop, 2016 Mar;155:25-33.
    PMID: 26658020 DOI: 10.1016/j.actatropica.2015.11.019
    Bartonella elizabethae has been known to cause endocarditis and neuroretinitis in humans. The genomic features and virulence profiles of a B. elizabethae strain (designated as BeUM) isolated from the spleen of a wild rat in Kuala Lumpur, Malaysia are described in this study. The BeUM strain has a genome size of 1,932,479bp and GC content of 38.3%. There is a high degree of conservation between the genomes of strain BeUM with B. elizabethae type strains (ATCC 49927 and F9251) and a rat-borne strain, Re6043vi. Of 2137 gene clusters identified from B. elizabethae strains, 2064 (96.6%) are indicated as the core gene clusters. Comparative genome analysis of B. elizabethae strains reveals virulence genes which are known in other pathogenic Bartonella species, including VirB2-11, vbhB2-B11, VirD4, trw, vapA2-5, hbpA-E, bepA-F, bepH, badA/vomp/brp, ialB, omp43/89 and korA-B. A putative intact prophage has been identified in the strain BeUM, in addition to a 8kb pathogenicity island. The whole genome analysis supports the zoonotic potential of the rodent-borne B. elizabethae, and provides basis for future functional and pathogenicity studies of B. elizabethae.
  11. Tan TK, Tan KY, Hari R, Mohamed Yusoff A, Wong GJ, Siow CC, et al.
    Database (Oxford), 2016;2016.
    PMID: 27616775 DOI: 10.1093/database/baw063
    Pangolins (order Pholidota) are the only mammals covered by scales. We have recently sequenced and analyzed the genomes of two critically endangered Asian pangolin species, namely the Malayan pangolin (Manis javanica) and the Chinese pangolin (Manis pentadactyla). These complete genome sequences will serve as reference sequences for future research to address issues of species conservation and to advance knowledge in mammalian biology and evolution. To further facilitate the global research effort in pangolin biology, we developed the Pangolin Genome Database (PGD), as a future hub for hosting pangolin genomic and transcriptomic data and annotations, and with useful analysis tools for the research community. Currently, the PGD provides the reference pangolin genome and transcriptome data, gene sequences and functional information, expressed transcripts, pseudogenes, genomic variations, organ-specific expression data and other useful annotations. We anticipate that the PGD will be an invaluable platform for researchers who are interested in pangolin and mammalian research. We will continue updating this hub by including more data, annotation and analysis tools particularly from our research consortium.Database URL: http://pangolin-genome.um.edu.my.
  12. Tan SY, Tan IK, Tan MF, Dutta A, Choo SW
    Sci Rep, 2016 10 31;6:36116.
    PMID: 27796355 DOI: 10.1038/srep36116
    On record, there are 17 species in the Yersinia genus, of which three are known to be pathogenic to human. While the chromosomal and pYV (or pCD1) plasmid-borne virulence genes as well as pathogenesis of these three species are well studied, their genomic evolution is poorly understood. Our study aims to predict the key evolutionary events that led to the emergence of pathogenic Yersinia species by analyzing gene gain-and-loss, virulence genes, and "Clustered regularly-interspaced short palindromic repeats". Our results suggest that the most recent ancestor shared by the human pathogenic Yersinia was most probably an environmental species that had adapted to the human body. This might have led to ecological specialization that diverged Yersinia into ecotypes and distinct lineages based on differential gene gain-and-loss in different niches. Our data also suggest that Y. pseudotuberculosis group might be the donor of the ail virulence gene to Y. enterocolitica. Hence, we postulate that evolution of human pathogenic Yersinia might not be totally in parallel, but instead, there were lateral gene transfer events. Furthermore, the presence of virulence genes seems to be important for the positive selection of virulence plasmid. Our studies provide better insights into the evolutionary biology of these bacteria.
  13. Tan SY, Dutta A, Jakubovics NS, Ang MY, Siow CC, Mutha NV, et al.
    BMC Bioinformatics, 2015;16:9.
    PMID: 25591325 DOI: 10.1186/s12859-014-0422-y
    Yersinia is a Gram-negative bacteria that includes serious pathogens such as the Yersinia pestis, which causes plague, Yersinia pseudotuberculosis, Yersinia enterocolitica. The remaining species are generally considered non-pathogenic to humans, although there is evidence that at least some of these species can cause occasional infections using distinct mechanisms from the more pathogenic species. With the advances in sequencing technologies, many genomes of Yersinia have been sequenced. However, there is currently no specialized platform to hold the rapidly-growing Yersinia genomic data and to provide analysis tools particularly for comparative analyses, which are required to provide improved insights into their biology, evolution and pathogenicity.
  14. Tan MF, Siow CC, Dutta A, Mutha NV, Wee WY, Heydari H, et al.
    BMC Genomics, 2015;16:755.
    PMID: 26444974 DOI: 10.1186/s12864-015-1959-5
    Listeria consists of both pathogenic and non-pathogenic species. Reports of similarities between the genomic content between some pathogenic and non-pathogenic species necessitates the investigation of these species at the genomic level to understand the evolution of virulence-associated genes. With Listeria genome data growing exponentially, comparative genomic analysis may give better insights into evolution, genetics and phylogeny of Listeria spp., leading to better management of the diseases caused by them.
  15. Tan KY, Dutta A, Tan TK, Hari R, Othman RY, Choo SW
    PeerJ, 2020;8:e9733.
    PMID: 32953261 DOI: 10.7717/peerj.9733
    Background: Paraburkholderia fungorum (P. fungorum) is a Gram-negative environmental species that has been commonly used as a beneficial microorganism in agriculture as an agent for biocontrol and bioremediation. Its use in agriculture is controversial as many people believe that it could harm human health; however, there is no clear evidence to support.

    Methodology: The pangolin P. fungorum (pangolin Pf) genome has a genomic size of approximately 7.7 Mbps with N50 of 69,666 bps. Our study showed that pangolin Pf is a Paraburkholderia fungorum supported by evidence from the core genome SNP-based phylogenetic analysis and the ANI analysis. Functional analysis has shown that the presence of a considerably large number of genes related to stress response, virulence, disease, and defence. Interestingly, we identified different types of secretion systems in the genome of pangolin Pf, which are highly specialized and responsible for a bacterium's response to its environment and in physiological processes such as survival, adhesion, and adaptation. The pangolin Pf also shared some common virulence genes with the known pathogenic member of the Burkholderiales. These genes play important roles in adhesion, motility, and invasion.

    Conclusion: This study may provide better insights into the functions, secretion systems and virulence of this pangolin-associated bacterial strain. The addition of this genome sequence is also important for future comparative analysis and functional work of P. fungorum.

  16. Tan KY, Deng S, Tan TK, Hari R, Sitam FT, Othman RY, et al.
    PeerJ, 2023;11:e16002.
    PMID: 37810781 DOI: 10.7717/peerj.16002
    BACKGROUND: The Malayan pangolin (Manis javanica) is a placental mammal and is listed as Critically Endangered on the IUCN Red List of Threatened Species. Most previous attempts to breed pangolins in captivity have met with little success because of dietary issues, infections, and other complications, although a previous study reported breeding pangolins in captivity to the third generation. In our previous pangolin genome sequencing data analysis, we obtained a considerable amount of bacterial DNA from a pregnant female Malayan pangolin (named "UM3"), which was likely infected by Paraburkholderia fungorum-an agent of biodegradation and bioremediation in agriculture.

    METHODOLOGY: Here, we further confirmed and characterized this bacterial species using PCR, histological staining, whole-genome sequencing, and bioinformatics approaches. PCR assays with in-house designed primer sets and 16S universal primers showed clear positive bands in the cerebrum, cerebellum, lung, and blood of UM3 suggesting that UM3 might have developed septicaemia. Histological staining showed the presence of Gram-negative rod-shaped bacteria in the pangolin brain and lungs, indicating the colonization of the bacteria in these two organs. In addition, PCR screening of UM3's fetal tissues revealed the presence of P. fungorum in the gastrocnemius muscle, but not in other tissues that we examined. We also sequenced and reconstructed the genome of pangolin P. fungorum, which has a genome size of 7.7 Mbps.

    CONCLUSION: Our study is the first to present detailed evidence of the presence of P. fungorum in a pangolin and her fetus (although preliminary results were presented in our previous article). Here, we raise the concern that P. fungorum may potentially infect humans, especially YOPI (young, old, pregnant, and immunocompromised) people. Therefore, caution should be exercised when using this bacterial species as biodegradation or bioremediation agents in agriculture.

  17. Tan JL, Ngeow YF, Wee WY, Wong GJ, Ng HF, Choo SW
    Sci Rep, 2014;4:7169.
    PMID: 25417557 DOI: 10.1038/srep07169
    Mycobacterium iranicum is a newly reported mycobacterial species. We present the first comparative study of M. iranicum UM_TJL and other mycobacteria. We found M. iranicum to have a close genetic association with environmental mycobacteria infrequently associated with human infections. Nonetheless, UM_TJL is also equipped with many virulence genes (some of which appear to be the consequence of transduction-related gene transfer) that have been identified in established human pathogens. Taken all together, our data suggest that M. iranicum is an environmental bacterium adapted for pathogenicity in the human host. This comparative study provides important clues and forms the basis for future functional studies on this mycobacterium.
  18. Tan JL, Khang TF, Ngeow YF, Choo SW
    BMC Genomics, 2013;14:879.
    PMID: 24330254 DOI: 10.1186/1471-2164-14-879
    Mycobacterium abscessus is a rapidly growing mycobacterium that is often associated with human infections. The taxonomy of this species has undergone several revisions and is still being debated. In this study, we sequenced the genomes of 12 M. abscessus strains and used phylogenomic analysis to perform subspecies classification.
  19. Tan JL, Ng HF, Wee WY, Ang MY, Wong GJ, Ngeow YF, et al.
    Genome Announc, 2013;1(5).
    PMID: 24072861 DOI: 10.1128/genomeA.00732-13
    Mycobacterium iranicum is a new species of nontuberculous mycobacterium reported in 2013. Here, we describe the first whole-genome sequence of this species, that of M. iranicum strain UM_TJL, isolated from a patient in Malaysia.
  20. Tan JL, Ngeow YF, Choo SW
    J Clin Microbiol, 2015 Sep;53(9):3042-6.
    PMID: 26157149 DOI: 10.1128/JCM.00541-15
    Mycobacterium abscessus subspecies classification has important clinical implications. We used phylogenomic network and amino acid analyses to provide evidence for the separation of Mycobacterium bolletii and Mycobacterium massiliense into two distinct subspecies which can potentially be differentiated rapidly by their protein signatures.
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