MyMedR

A collective statement in support of saving pangolins

Choo SW, Chong JL, Gaubert P, Hughes AC, O'Brien S, Chaber AL, et al.

Sci Total Environ, 2022 Feb 14.

PMID: 35176378 DOI: 10.1016/j.scitotenv.2022.153666

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.

Analysis of the genome of Mycobacterium abscessus strain M94 reveals an uncommon cluster of tRNAs

Choo SW, Wong YL, Leong ML, Heydari H, Ong CS, Ng KP, et al.

J Bacteriol, 2012 Oct;194(20):5724.

PMID: 23012295

Mycobacterium abscessus is a species of rapidly growing nontuberculous mycobacteria that is frequently associated with opportunistic infections in humans. Here, we report the annotated genome sequence of M. abscessus strain M94, which showed an unusual cluster of tRNAs.

Fulltext Annotated genome sequence of Mycobacterium massiliense strain M154, belonging to the recently created taxon Mycobacterium abscessus subsp. bolletii comb. nov

Choo SW, Wong YL, Tan JL, Ong CS, Wong GJ, Ng KP, et al.

J Bacteriol, 2012 Sep;194(17):4778.

PMID: 22887675 DOI: 10.1128/JB.01043-12

Mycobacterium massiliense has recently been proposed as a member of Mycobacterium abscessus subsp. bolletii comb. nov. Strain M154, a clinical isolate from the bronchoalveolar lavage fluid of a Malaysian patient presenting with lower respiratory tract infection, was subjected to shotgun DNA sequencing with the Illumina sequencing technology to obtain whole-genome sequence data for comparison with other genetically related strains within the M. abscessus species complex.

Fulltext Characterisation of Drosophila Ubx CPTI000601 and hth CPTI000378 protein trap lines

Choo SW, Beh CY, Russell S, White R

ScientificWorldJournal, 2014;2014:191535.

PMID: 25389534 DOI: 10.1155/2014/191535

In Drosophila, protein trap strategies provide powerful approaches for the generation of tagged proteins expressed under endogenous control. Here, we describe expression and functional analysis to evaluate new Ubx and hth protein trap lines generated by the Cambridge Protein Trap project. Both protein traps exhibit spatial and temporal expression patterns consistent with the reported endogenous pattern in the embryo. In imaginal discs, Ubx-YFP is expressed throughout the haltere and 3rd leg imaginal discs, while Hth-YFP is expressed in the proximal regions of haltere and wing discs but not in the pouch region. The Ubx (CPTI000601) line is semilethal as a homozygote. No T3/A1 to T2 transformations were observed in the embryonic cuticle or the developing midgut. The homozygous survivors, however, exhibit a weak haltere phenotype with a few wing-like marginal bristles on the haltere capitellum. Although hth (CPTI000378) is completely lethal as a homozygote, the hth (CPTI000378) /hth (C1) genotype is viable. Using a hth deletion (Df(3R)BSC479) we show that hth (CPTI000378) /Df(3R)BSC479 adults are phenotypically normal. No transformations were observed in hth (CPTI000378), hth (CPTI000378) /hth (C1), or hth (CPTI000378) /Df(3R)BSC479 embryonic cuticles. We have successfully characterised the Ubx-YFP and Hth-YFP protein trap lines demonstrating that the tagged proteins show appropriate expression patterns and produce at least partially functional proteins.

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.

Fulltext Comparative Genomic Analysis Reveals a Possible Novel Non-Tuberculous Mycobacterium Species with High Pathogenic Potential

Choo SW, Dutta A, Wong GJ, Wee WY, Ang MY, Siow CC

PLoS One, 2016;11(4):e0150413.

PMID: 27035710 DOI: 10.1371/journal.pone.0150413

Mycobacteria have been reported to cause a wide range of human diseases. We present the first whole-genome study of a Non-Tuberculous Mycobacterium, Mycobacterium sp. UM_CSW (referred to hereafter as UM_CSW), isolated from a patient diagnosed with bronchiectasis. Our data suggest that this clinical isolate is likely a novel mycobacterial species, supported by clear evidence from molecular phylogenetic, comparative genomic, ANI and AAI analyses. UM_CSW is closely related to the Mycobacterium avium complex. While it has characteristic features of an environmental bacterium, it also shows a high pathogenic potential with the presence of a wide variety of putative genes related to bacterial virulence and shares very similar pathogenomic profiles with the known pathogenic mycobacterial species. Thus, we conclude that this possible novel Mycobacterium species should be tightly monitored for its possible causative role in human infections.

Fulltext Comparative genome analyses of Mycobacteroides immunogenum reveals two potential novel subspecies

Choo SW, Rishik S, Wee WY

Microb Genom, 2020 12;6(12).

PMID: 33295861 DOI: 10.1099/mgen.0.000495

Mycobacteroides immunogenum is an emerging opportunistic pathogen implicated in nosocomial infections. Comparative genome analyses may provide better insights into its genomic structure, functions and evolution. The present analysis showed that M. immunogenum has an open pan-genome. Approximately 36.8% of putative virulence genes were identified in the accessory regions of M. immunogenum. Phylogenetic analyses revealed two potential novel subspecies of M. immunogenum, supported by evidence from ANIb (average nucleotide identity using blast) and GGDC (Genome to Genome Distance Calculator) analyses. We identified 74 genomic islands (GIs) in Subspecies 1 and 23 GIs in Subspecies 2. All Subspecies 2-harboured GIs were not found in Subspecies 1, indicating that they might have been acquired by Subspecies 2 after their divergence. Subspecies 2 has more defence genes than Subspecies 1, suggesting that it might be more resistant to the insertion of foreign DNA and probably explaining why Subspecies 2 has fewer GIs. Positive selection analysis suggest that M. immunogenum has a lower selection pressure compared to non-pathogenic mycobacteria. Thirteen genes were positively selected and many were involved in virulence.

Fulltext Comparative genome analyses of mycobacteria give better insights into their evolution

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.

Fulltext Comparative genome sequencing and analyses of Mycobacterium cosmeticum reveal potential for biodesulfization of gasoline

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.

Fulltext Comparative genomic analysis of Mycobacterium iranicum UM_TJL against representative mycobacterial species suggests its environmental origin

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.

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.

Fulltext Comprehensive genome analysis of a pangolin-associated Paraburkholderia fungorum provides new insights into its secretion systems and virulence

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.

Fulltext CoryneBase: Corynebacterium genomic resources and analysis tools at your fingertips

Heydari H, Siow CC, Tan MF, Jakubovics NS, Wee WY, Mutha NV, et al.

PLoS One, 2014;9(1):e86318.

PMID: 24466021 DOI: 10.1371/journal.pone.0086318

Corynebacteria are used for a wide variety of industrial purposes but some species are associated with human diseases. With increasing number of corynebacterial genomes having been sequenced, comparative analysis of these strains may provide better understanding of their biology, phylogeny, virulence and taxonomy that may lead to the discoveries of beneficial industrial strains or contribute to better management of diseases. To facilitate the ongoing research of corynebacteria, a specialized central repository and analysis platform for the corynebacterial research community is needed to host the fast-growing amount of genomic data and facilitate the analysis of these data. Here we present CoryneBase, a genomic database for Corynebacterium with diverse functionality for the analysis of genomes aimed to provide: (1) annotated genome sequences of Corynebacterium where 165,918 coding sequences and 4,180 RNAs can be found in 27 species; (2) access to comprehensive Corynebacterium data through the use of advanced web technologies for interactive web interfaces; and (3) advanced bioinformatic analysis tools consisting of standard BLAST for homology search, VFDB BLAST for sequence homology search against the Virulence Factor Database (VFDB), Pairwise Genome Comparison (PGC) tool for comparative genomic analysis, and a newly designed Pathogenomics Profiling Tool (PathoProT) for comparative pathogenomic analysis. CoryneBase offers the access of a range of Corynebacterium genomic resources as well as analysis tools for comparative genomics and pathogenomics. It is publicly available at http://corynebacterium.um.edu.my/.

Fulltext De novo sequencing, assembly and analysis of eight different transcriptomes from the Malayan pangolin

Mohamed Yusoff A, Tan TK, Hari R, Koepfli KP, Wee WY, Antunes A, et al.

Sci Rep, 2016 09 13;6:28199.

PMID: 27618997 DOI: 10.1038/srep28199

Pangolins are scale-covered mammals, containing eight endangered species. Maintaining pangolins in captivity is a significant challenge, in part because little is known about their genetics. Here we provide the first large-scale sequencing of the critically endangered Manis javanica transcriptomes from eight different organs using Illumina HiSeq technology, yielding ~75 Giga bases and 89,754 unigenes. We found some unigenes involved in the insect hormone biosynthesis pathway and also 747 lipids metabolism-related unigenes that may be insightful to understand the lipid metabolism system in pangolins. Comparative analysis between M. javanica and other mammals revealed many pangolin-specific genes significantly over-represented in stress-related processes, cell proliferation and external stimulus, probably reflecting the traits and adaptations of the analyzed pregnant female M. javanica. Our study provides an invaluable resource for future functional works that may be highly relevant for the conservation of pangolins.

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.

Fulltext Distinct Biological Potential of Streptococcus gordonii and Streptococcus sanguinis Revealed by Comparative Genome Analysis

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.

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 Draft genome sequence of Mycobacterium bolletii strain M24, a rapidly growing mycobacterium of contentious taxonomic status

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.

Draft genome sequence of a marine actinobacteria Sciscionella strain SE31

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.

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