MyMedR

Whole-genome sequence analysis and exploration of the zoonotic potential of a rat-borne Bartonella elizabethae

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.

Transcriptomic Responses to Coaggregation between Streptococcus gordonii and Streptococcus oralis

Choo SW, Mohammed WK, Mutha NVR, Rostami N, Ahmed H, Krasnogor N, et al.

Appl Environ Microbiol, 2021 10 28;87(22):e0155821.

PMID: 34469191 DOI: 10.1128/AEM.01558-21

Cell-cell adhesion between oral bacteria plays a key role in the development of polymicrobial communities such as dental plaque. Oral streptococci such as Streptococcus gordonii and Streptococcus oralis are important early colonizers of dental plaque and bind to a wide range of different oral microorganisms, forming multispecies clumps or "coaggregates." S. gordonii actively responds to coaggregation by regulating gene expression. To further understand these responses, we assessed gene regulation in S. gordonii and S. oralis following coaggregation in 25% human saliva. Coaggregates were formed by mixing, and after 30 min, RNA was extracted for dual transcriptome sequencing (RNA-Seq) analysis. In S. oralis, 18 genes (6 upregulated and 12 downregulated) were regulated by coaggregation. Significantly downregulated genes encoded functions such as amino acid and antibiotic biosynthesis, ribosome, and central carbon metabolism. In total, 28 genes were differentially regulated in Streptococcus gordonii (25 upregulated and 3 downregulated). Many genes associated with transporters and a two-component (NisK/SpaK) regulatory system were upregulated following coaggregation. Our comparative analyses of S. gordonii-S. oralis with different previously published S. gordonii pairings (S. gordonii-Fusobacterium nucleatum and S. gordonii-Veillonella parvula) suggest that the gene regulation is specific to each pairing, and responses do not appear to be conserved. This ability to distinguish between neighboring bacteria may be important for S. gordonii to adapt appropriately during the development of complex biofilms such as dental plaque. IMPORTANCE Dental plaque is responsible for two of the most prevalent diseases in humans, dental caries and periodontitis. Controlling the formation of dental plaque and preventing the transition from oral health to disease requires a detailed understanding of microbial colonization and biofilm development. Streptococci are among the most common colonizers of dental plaque. This study identifies key genes that are regulated when oral streptococci bind to one another, as they do in the early stages of dental plaque formation. We show that specific genes are regulated in two different oral streptococci following the formation of mixed-species aggregates. The specific responses of S. gordonii to coaggregation with S. oralis are different from those to coaggregation with other oral bacteria. Targeting the key genes that are upregulated during interspecies interactions may be a powerful approach to control the development of biofilm and maintain oral health.

Fulltext YersiniaBase: a genomic resource and analysis platform for comparative analysis of Yersinia

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.

Fulltext HelicoBase: a Helicobacter genomic resource and analysis platform

Choo SW, Ang MY, Fouladi H, Tan SY, Siow CC, Mutha NV, et al.

BMC Genomics, 2014;15:600.

PMID: 25030426 DOI: 10.1186/1471-2164-15-600

Helicobacter is a genus of Gram-negative bacteria, possessing a characteristic helical shape that has been associated with a wide spectrum of human diseases. Although much research has been done on Helicobacter and many genomes have been sequenced, currently there is no specialized Helicobacter genomic resource and analysis platform to facilitate analysis of these genomes. With the increasing number of Helicobacter genomes being sequenced, comparative genomic analysis on members of this species will provide further insights on their taxonomy, phylogeny, pathogenicity and other information that may contribute to better management of diseases caused by Helicobacter pathogens.

Fulltext A phylogenomic approach to bacterial subspecies classification: proof of concept in Mycobacterium abscessus

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.

Fulltext Development of ListeriaBase and comparative analysis of Listeria monocytogenes

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.

Genome characterization and taxonomy of Actinomyces acetigenes sp. nov., and Actinomyces stomatis sp. nov., previously isolated from the human oral cavity

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.

Fulltext FusoBase: an online Fusobacterium comparative genomic analysis platform

Ang MY, Heydari H, Jakubovics NS, Mahmud MI, Dutta A, Wee WY, et al.

Database (Oxford), 2014;2014.

PMID: 25149689 DOI: 10.1093/database/bau082

Fusobacterium are anaerobic gram-negative bacteria that have been associated with a wide spectrum of human infections and diseases. As the biology of Fusobacterium is still not well understood, comparative genomic analysis on members of this species will provide further insights on their taxonomy, phylogeny, pathogenicity and other information that may contribute to better management of infections and diseases. To facilitate the ongoing genomic research on Fusobacterium, a specialized database with easy-to-use analysis tools is necessary. Here we present FusoBase, an online database providing access to genome-wide annotated sequences of Fusobacterium strains as well as bioinformatics tools, to support the expanding scientific community. Using our custom-developed Pairwise Genome Comparison tool, we demonstrate how differences between two user-defined genomes and how insertion of putative prophages can be identified. In addition, Pathogenomics Profiling Tool is capable of clustering predicted genes across Fusobacterium strains and visualizing the results in the form of a heat map with dendrogram.

Fulltext StaphyloBase: a specialized genomic resource for the staphylococcal research community

Heydari H, Mutha NV, Mahmud MI, Siow CC, Wee WY, Wong GJ, et al.

Database (Oxford), 2014;2014:bau010.

PMID: 24578355 DOI: 10.1093/database/bau010

With the advent of high-throughput sequencing technologies, many staphylococcal genomes have been sequenced. Comparative analysis of these strains will provide better understanding of their biology, phylogeny, virulence and taxonomy, which may contribute to better management of diseases caused by staphylococcal pathogens. We developed StaphyloBase with the goal of having a one-stop genomic resource platform for the scientific community to access, retrieve, download, browse, search, visualize and analyse the staphylococcal genomic data and annotations. We anticipate this resource platform will facilitate the analysis of staphylococcal genomic data, particularly in comparative analyses. StaphyloBase currently has a collection of 754 032 protein-coding sequences (CDSs), 19 258 rRNAs and 15 965 tRNAs from 292 genomes of different staphylococcal species. Information about these features is also included, such as putative functions, subcellular localizations and gene/protein sequences. Our web implementation supports diverse query types and the exploration of CDS- and RNA-type information in detail using an AJAX-based real-time search system. JBrowse has also been incorporated to allow rapid and seamless browsing of staphylococcal genomes. The Pairwise Genome Comparison tool is designed for comparative genomic analysis, for example, to reveal the relationships between two user-defined staphylococcal genomes. A newly designed Pathogenomics Profiling Tool (PathoProT) is also included in this platform to facilitate comparative pathogenomics analysis of staphylococcal strains. In conclusion, StaphyloBase offers access to a range of staphylococcal genomic resources as well as analysis tools for comparative analyses. Database URL: http://staphylococcus.um.edu.my/.

Fulltext PGD: a pangolin genome hub for the research community

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.

Fulltext Roles of cofactors and chromatin accessibility in Hox protein target specificity

Beh CY, El-Sharnouby S, Chatzipli A, Russell S, Choo SW, White R

Epigenetics Chromatin, 2016;9:1.

PMID: 26753000 DOI: 10.1186/s13072-015-0049-x

The regulation of specific target genes by transcription factors is central to our understanding of gene network control in developmental and physiological processes yet how target specificity is achieved is still poorly understood. This is well illustrated by the Hox family of transcription factors as their limited in vitro DNA-binding specificity contrasts with their clear in vivo functional specificity.

Fulltext Genome Sequence of Parvimonas micra Strain A293, Isolated from an Abdominal Abscess from a Patient in the United Kingdom

Ang MY, Dymock D, Tan JL, Thong MH, Tan QK, Wong GJ, et al.

Genome Announc, 2013;1(6).

PMID: 24309744 DOI: 10.1128/genomeA.01025-13

Parvimonas micra is an important oral microbe that has the ability to grow and proliferate within oral biofilms and is involved in periodontal disease, leading to gingival bleeding, gingival recession, alveolar bone loss, and tooth mobility. However, occasionally these normally oral pathogens can cause infections at other sites in the body. We present the genome sequence of Parvimonas micra strain A293, a smooth Parvimonas micra strain isolated from an abdominal abscess from a patient at Barts Hospital, London, United Kingdom.

Fulltext Genome Sequence of Fusobacterium nucleatum Strain W1481, a Possible New Subspecies Isolated from a Periodontal Pocket

Ang MY, Dymock D, Tan JL, Thong MH, Tan QK, Wong GJ, et al.

Genome Announc, 2014;2(1).

PMID: 24526626 DOI: 10.1128/genomeA.00009-14

Fusobacterium nucleatum is a bacterial species commonly detected in dental plaque within the human oral cavity, with some strains associated with periodontal disease, one of the most common clinical bacterial infections in the human body. The exact mechanisms of its pathogenesis are still not completely understood. In this study, we present the genome sequence and annotation of F. nucleatum strain W1481, isolated from a periodontal pocket of a dental patient at the University of Bristol, United Kingdom, the 16S rRNA gene sequencing of which showed it to be markedly different from the five previously named subspecies.

Fulltext First Whole-Genome Sequence of Mycobacterium iranicum, a Newly Reported Mycobacterial Species

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.

Fulltext Draft Genome Sequence of Mycobacterium massiliense Strain M159, Showing Phenotypic Resistance to β-Lactam and Tetracycline Antibiotics

Ngeow YF, Leong ML, Wong YL, Wong GJ, Tan JL, Wee WY, et al.

Genome Announc, 2013;1(4).

PMID: 23990576 DOI: 10.1128/genomeA.00669-13

Mycobacterium massiliense is a nontuberculous mycobacterium associated with human infections. We report here the draft genome sequence of M. massiliense strain M159, isolated from the bronchial aspirate of a patient who had a pulmonary infection. This strain showed genotypic and in vitro resistance to a number of tetracyclines and beta-lactam antibiotics.

Fulltext Metagenomic sequencing of prokaryotic microbiota from tropical surface seawater

Chan XY, Arumugam R, Choo SW, Yin WF, Chan KG

Genome Announc, 2013;1(4).

PMID: 23950114 DOI: 10.1128/genomeA.00540-13

Tropical seawater harbors a rich diversity of microorganisms as a result of its nutrient-rich environment, constant supply of sufficient sunlight, and warm climate. In this report, we present the complexity of the microbial diversity of the surface seawater of the Georgetown coast as determined using next-generation sequencing technology.

Fulltext Whole-Genome Shotgun Sequencing of Mycobacterium abscessus M156, an Emerging Clinical Pathogen in Malaysia

Choo SW, Wong YL, Beh CY, Lokanathan N, Leong ML, Ong CS, et al.

Genome Announc, 2013 Jan;1(1).

PMID: 23405341 DOI: 10.1128/genomeA.00063-12

Mycobacterium abscessus is an emerging clinical pathogen commonly associated with non-tuberculous mycobacterial infections. We report herein the draft genome of M. abscessus strain M156.

Comparative Genome Analysis of Fusobacterium nucleatum

Ang MY, Dutta A, Wee WY, Dymock D, Paterson IC, Choo SW

Genome Biol Evol, 2016 10 05;8(9):2928-2938.

PMID: 27540086

Fusobacterium nucleatum is considered to be a key oral bacterium in recruiting periodontal pathogens into subgingival dental plaque. Currently F. nucleatum can be subdivided into five subspecies. Our previous genome analysis of F. nucleatum W1481 (referred to hereafter as W1481), isolated from an 8-mm periodontal pocket in a patient with chronic periodontitis, suggested the possibility of a new subspecies. To further investigate the biology and relationships of this possible subspecies with other known subspecies, we performed comparative analysis between W1481 and 35 genome sequences represented by the five known Fusobacterium subspecies. Our analyses suggest that W1481 is most likely a new F. nucleatum subspecies, supported by evidence from phylogenetic analyses and maximal unique match indices (MUMi). Interestingly, we found a horizontally transferred W1481-specific genomic island harboring the tripartite ATP-independent (TRAP)-like transporter genes, suggesting this bacterium might have a high-affinity transport system for the C4-dicarboxylates malate, succinate, and fumarate. Moreover, we found virulence genes in the W1481 genome that may provide a strong defense mechanism which might enable it to colonize and survive within the host by evading immune surveillance. This comparative study provides better understanding of F. nucleatum and the basis for future functional work on this important pathogen.

Pangolin genomes and the evolution of mammalian scales and immunity

Choo SW, Rayko M, Tan TK, Hari R, Komissarov A, Wee WY, et al.

Genome Res, 2016 10;26(10):1312-1322.

PMID: 27510566

Pangolins, unique mammals with scales over most of their body, no teeth, poor vision, and an acute olfactory system, comprise the only placental order (Pholidota) without a whole-genome map. To investigate pangolin biology and evolution, we developed genome assemblies of the Malayan (Manis javanica) and Chinese (M. pentadactyla) pangolins. Strikingly, we found that interferon epsilon (IFNE), exclusively expressed in epithelial cells and important in skin and mucosal immunity, is pseudogenized in all African and Asian pangolin species that we examined, perhaps impacting resistance to infection. We propose that scale development was an innovation that provided protection against injuries or stress and reduced pangolin vulnerability to infection. Further evidence of specialized adaptations was evident from positively selected genes involving immunity-related pathways, inflammation, energy storage and metabolism, muscular and nervous systems, and scale/hair development. Olfactory receptor gene families are significantly expanded in pangolins, reflecting their well-developed olfaction system. This study provides insights into mammalian adaptation and functional diversification, new research tools and questions, and perhaps a new natural IFNE-deficient animal model for studying mammalian immunity.

Fulltext Comparing the genomes of Helicobacter pylori clinical strain UM032 and Mice-adapted derivatives

Khosravi Y, Rehvathy V, Wee WY, Wang S, Baybayan P, Singh S, et al.

Gut Pathog, 2013;5:25.

PMID: 23957912 DOI: 10.1186/1757-4749-5-25

Helicobacter pylori is a Gram-negative bacterium that persistently infects the human stomach inducing chronic inflammation. The exact mechanisms of pathogenesis are still not completely understood. Although not a natural host for H. pylori, mouse infection models play an important role in establishing the immunology and pathogenicity of H. pylori. In this study, for the first time, the genome sequences of clinical H. pylori strain UM032 and mice-adapted derivatives, 298 and 299, were sequenced using the PacBio Single Molecule, Real-Time (SMRT) technology.

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