Publications by authors named "Li Mei Pang"

10 Publications

  • Page 1 of 1

Role of the oral microbiome, metabolic pathways, and novel diagnostic tools in intra-oral halitosis: a comprehensive update.

Crit Rev Microbiol 2021 Mar 3:1-17. Epub 2021 Mar 3.

Oral Health ACP, Duke NUS Medical School, Singapore, Singapore.

Halitosis or oral malodor is one of the most common reasons for the patients' visit to the dental clinic, ranking behind only dental caries and periodontitis. In the present times, where social and professional communications are becoming unavoidable, halitosis has become a concern of growing importance. Oral malodor mostly develops due to the putrefaction of substrates by the indigenous bacterial populations. Although culture-based studies have provided adequate information on halitosis, the high throughput omics technologies have amplified the resolution at which oral microbial community can be examined and has led to the detection of a broader range of taxa associated with intra-oral halitosis (IOH). These microorganisms are regulated by the interactions of their ecological processes. Thus to develop effective treatment strategies, it is important to understand the microbial basis of halitosis. In the current review, we provide an update on IOH in context to the role of the oral microbiome, metabolic pathways involved, and novel diagnostic tools, including breathomics. Understanding oral microbiota associated with halitosis from a broader ecological perspective can provide novel insights into one's oral and systemic health. Such information can pave the way for the emergence of diagnostic tools that can revolutionize the early detection of halitosis and various associated medical conditions.
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http://dx.doi.org/10.1080/1040841X.2021.1888867DOI Listing
March 2021

The Proteome of Community Living Is Differentially Modulated by the Morphologic and Structural Features of the Bacterial Cohabitants.

Microorganisms 2020 Oct 7;8(10). Epub 2020 Oct 7.

National Dental Research Institute Singapore (NDRIS), National Dental Centre Singapore, Singapore 168938, Singapore.

is a commensal polymorphic and opportunistic fungus, which usually resides as a small community in the oral cavities of a majority of humans. The latter eco-system presents this yeast varied opportunities for mutualistic interactions with other cohabitant oral bacteria, that synergizes its persistence and pathogenicity. Collectively, these communities live within complex plaque biofilms which may adversely affect the oral health and increase the proclivity for oral candidiasis. The proteome of such oral biofilms with myriad interkingdom interactions are largely underexplored. Herein, we employed limma differential expression analysis, and cluster analysis to explore the proteomic interactions of biofilms with nine different common oral bacterial species, , , , , , , , , and . Interestingly, upon exposure of biofilms to the foregoing heat-killed bacteria, the proteomes of the fungus associated with cellular respiration, translation, oxidoreductase activity, and ligase activity were significantly altered. Subsequent differential expression and cluster analysis revealed the subtle, yet significant alterations in the proteome, particularly on exposure to bacteria with dissimilar cell morphologies, and Gram staining characteristics.
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http://dx.doi.org/10.3390/microorganisms8101541DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7601143PMC
October 2020

Correction: Discovery, biosynthesis and antifungal mechanism of the polyene-polyol meijiemycin.

Chem Commun (Camb) 2020 01 3;56(5):826. Epub 2020 Jan 3.

School of Biological Sciences, Nanyang Technological University, 637551, Singapore. and The Singapore Centre for Environmental Life Sciences Engineering (SCELSE), Nanyang Technological University, 637551, Singapore.

Correction for 'Discovery, biosynthesis and antifungal mechanism of the polyene-polyol meijiemycin' by Zhen Jie Low et al., Chem. Commun., 2020, DOI: .
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http://dx.doi.org/10.1039/c9cc90554eDOI Listing
January 2020

Discovery, biosynthesis and antifungal mechanism of the polyene-polyol meijiemycin.

Chem Commun (Camb) 2020 01 18;56(5):822-825. Epub 2019 Dec 18.

School of Biological Sciences, Nanyang Technological University, 637551, Singapore. and The Singapore Centre for Environmental Life Sciences Engineering (SCELSE), Nanyang Technological University, 637551, Singapore.

Produced by a newly isolated Streptomycetes strain, meijiemycin is a gigantic linear polyene-polyol that exhibits structural features not seen in other members of the polyene-polyol family. We propose a biosynthetic mechanism and demonstrate that meijiemycin inhibits hyphal growth by inducing the aggregation of ergosterol and restructuring of the fungal plasma membrane.
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http://dx.doi.org/10.1039/c9cc08908jDOI Listing
January 2020

Proteomics Analysis of Candida albicans dnm1 Haploid Mutant Unraveled the Association between Mitochondrial Fission and Antifungal Susceptibility.

Proteomics 2020 01 18;20(1):e1900240. Epub 2019 Dec 18.

National Dental Research Institute Singapore, Singhealth Duke NUS, Singapore, 5 Second Hospital Ave, Singapore, 168938.

Candida albicans is a major fungal pathogen, accounting for approximately 15% of healthcare infections with associated mortality as high as 40% in the case of systemic candidiasis. Antifungal agents for C. albicans infections are limited, and rising resistance is an inevitable problem. Therefore, understanding the mechanism behind antifungal responses is among the top research focuses in combating Candida infections. Herein, the recently developed C. albicans haploid model is employed to examine the association between mitochondrial fission, regulated by Dnm1, and the pathogen's response to antifungals. Proteomic analysis of dnm1Δ and its wild-type haploid parent, GZY803, reveal changes in proteins associated with mitochondrial structures and functions, cell wall, and plasma membrane. Antifungal susceptibility testing revealed that dnm1Δ is more susceptible to SM21, a novel antifungal, than GZY803. Analyses of reactive oxygen species release, antioxidant response, lipid peroxidation, and membrane damages uncover an association between dnm1Δ and the susceptibility to SM21. Dynasore-induced mitochondrial inhibition in SC5314 diploids corroborate the findings. Interestingly, Dynasore-primed SC5314 cultures exhibit increased susceptibility to all antifungals tested. These data suggest an important contribution of mitochondrial fission in antifungal susceptibility of C. albicans. Hence, mitochondrial fission can be a potential target for combined therapy in anti-C. albicans treatment.
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http://dx.doi.org/10.1002/pmic.201900240DOI Listing
January 2020

Integrated Genomic and Metabolomic Approach to the Discovery of Potential Anti-Quorum Sensing Natural Products from Microbes Associated with Marine Samples from Singapore.

Mar Drugs 2019 Jan 21;17(1). Epub 2019 Jan 21.

Natural Sciences and Science Education, National Institute of Education, Nanyang Technological University, 1 Nanyang Walk, Singapore 637616, Singapore.

With 70% of the Earth's surface covered in water, the marine ecosystem offers immense opportunities for drug discovery and development. Due to the decreasing rate of novel natural product discovery from terrestrial sources in recent years, many researchers are beginning to look seaward for breakthroughs in new therapeutic agents. As part of an ongoing marine drug discovery programme in Singapore, an integrated approach of combining metabolomic and genomic techniques were initiated for uncovering novel anti-quorum sensing molecules from bacteria associated with subtidal samples collected in the Singapore Strait. Based on the culture-dependent method, a total of 102 marine bacteria strains were isolated and the identities of selected strains were established based on their 16S rRNA gene sequences. About 5% of the marine bacterial organic extracts showed quorum sensing inhibitory (QSI) activity in a dose-dependent manner based on the QS reporter system. In addition, the extracts were subjected to mass spectrometry-based molecular networking and the genome of selected strains were analysed for known as well as new biosynthetic gene clusters. This study revealed that using integrated techniques, coupled with biological assays, can provide an effective and rapid prioritization of marine bacterial strains for downstream large-scale culturing for the purpose of isolation and structural elucidation of novel bioactive compounds.
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http://dx.doi.org/10.3390/md17010072DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6356914PMC
January 2019

MS/MS-Based Molecular Networking Approach for the Detection of Aplysiatoxin-Related Compounds in Environmental Marine Cyanobacteria.

Mar Drugs 2018 Dec 13;16(12). Epub 2018 Dec 13.

Natural Sciences and Science Education, National Institute of Education, Nanyang Technological University, Singapore 637616, Singapore.

Certain strains of cyanobacteria produce a wide array of cyanotoxins, such as microcystins, lyngbyatoxins and aplysiatoxins, that are associated with public health issues. In this pilot study, an approach combining LC-MS/MS and molecular networking was employed as a rapid analytical method to detect aplysiatoxins present in four environmental marine cyanobacterial samples collected from intertidal areas in Singapore. Based on 16S-ITS rRNA gene sequences, these filamentous cyanobacterial samples collected from Pulau Hantu were determined as , sp. PAB-2 and sp. PNG05-4. Organic extracts were prepared and analyzed on LC-HRMS/MS and Global Natural Product Social Molecular Networking (GNPS) for the presence of aplysiatoxin-related molecules. From the molecular networking, six known compounds, debromoaplysiatoxin (), anhydrodebromoaplysiatoxin (), 3-methoxydebromoaplysiatoxin (), aplysiatoxin (), oscillatoxin A () and 31-noroscillatoxin B (), as well as potential new analogues, were detected in these samples. In addition, differences and similarities in molecular networking clusters related to the aplysiatoxin molecular family were observed in extracts of collected from two different locations and from different cyanobacterial species found at Pulau Hantu, respectively.
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http://dx.doi.org/10.3390/md16120505DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6315786PMC
December 2018

Identification of a biosynthetic gene cluster for the polyene macrolactam sceliphrolactam in a Streptomyces strain isolated from mangrove sediment.

Sci Rep 2018 01 25;8(1):1594. Epub 2018 Jan 25.

School of Biological Sciences, Nanyang Technological University, Singapore, 637551, Singapore.

Streptomyces are a genus of Actinobacteria capable of producing structurally diverse natural products. Here we report the isolation and characterization of a biosynthetically talented Streptomyces (Streptomyces sp. SD85) from tropical mangrove sediments. Whole-genome sequencing revealed that Streptomyces sp. SD85 harbors at least 52 biosynthetic gene clusters (BGCs), which constitute 21.2% of the 8.6-Mb genome. When cultivated under lab conditions, Streptomyces sp. SD85 produces sceliphrolactam, a 26-membered polyene macrolactam with unknown biosynthetic origin. Genome mining yielded a putative sceliphrolactam BGC (sce) that encodes a type I modular polyketide synthase (PKS) system, several β-amino acid starter biosynthetic enzymes, transporters, and transcriptional regulators. Using the CRISPR/Cas9-based gene knockout method, we demonstrated that the sce BGC is essential for sceliphrolactam biosynthesis. Unexpectedly, the PKS system encoded by sce is short of one module required for assembling the 26-membered macrolactam skeleton according to the collinearity rule. With experimental data disfavoring the involvement of a trans-PKS module, the biosynthesis of sceliphrolactam seems to be best rationalized by invoking a mechanism whereby the PKS system employs an iterative module to catalyze two successive chain extensions with different outcomes. The potential violation of the collinearity rule makes the mechanism distinct from those of other polyene macrolactams.
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http://dx.doi.org/10.1038/s41598-018-20018-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5785472PMC
January 2018

N-Lipidated Peptide Dimers: Effective Antibacterial Agents against Gram-Negative Pathogens through Lipopolysaccharide Permeabilization.

J Med Chem 2015 Aug 12;58(16):6533-48. Epub 2015 Aug 12.

Singapore Eye Research Institute, The Academia , 20 College Road, Discovery Tower Level 6, 169856, Singapore.

Treating infections caused by multidrug-resistant Gram-negative pathogens is challenging, and there is concern regarding the toxicity of the most effective antimicrobials for Gram-negative pathogens. We hypothesized that conjugating a fatty acid moiety onto a peptide dimer could maximize the interaction with lipopolysaccharide (LPS) and facilitate the permeabilization of the LPS barrier, thereby improving potency against Gram-negative pathogens. We systematically designed a series of N-lipidated peptide dimers that are active against Gram-negative bacteria, including carbapenem-resistant Enterobacteriaceae (CRE). The optimized lipid length was 6-10 carbons. At these lipid lengths, the N-lipidated peptide dimers exhibited strong LPS permeabilization. Compound 23 exhibited synergy with select antibiotics in most of the combinations tested. 23 and 32 also displayed rapid bactericidal activity. Importantly, 23 and 32 were nonhemolytic at 10 mg/mL, with no cellular or in vivo toxicity. These characteristics suggest that these compounds can overcome the limitations of current Gram-negative-targeted antimicrobials such as polymyxin B.
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http://dx.doi.org/10.1021/acs.jmedchem.5b00628DOI Listing
August 2015

Amino acid modified xanthone derivatives: novel, highly promising membrane-active antimicrobials for multidrug-resistant Gram-positive bacterial infections.

J Med Chem 2015 Jan 17;58(2):739-52. Epub 2014 Dec 17.

Singapore Eye Research Institute , 11 Third Hospital Avenue, 168751, Singapore.

Antibiotic resistance is a critical global health care crisis requiring urgent action to develop more effective antibiotics. Utilizing the hydrophobic scaffold of xanthone, we identified three components that mimicked the action of an antimicrobial cationic peptide to produce membrane-targeting antimicrobials. Compounds 5c and 6, which contain a hydrophobic xanthone core, lipophilic chains, and cationic amino acids, displayed very promising antimicrobial activity against multidrug-resistant Gram-positive bacteria, including MRSA and VRE, rapid time-kill, avoidance of antibiotic resistance, and low toxicity. The bacterial membrane selectivity of these molecules was comparable to that of several membrane-targeting antibiotics in clinical trials. 5c and 6 were effective in a mouse model of corneal infection by S. aureus and MRSA. Evidence is presented indicating that 5c and 6 target the negatively charged bacterial membrane via a combination of electrostatic and hydrophobic interactions. These results suggest that 5c and 6 have significant promise for combating life-threatening infections.
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http://dx.doi.org/10.1021/jm501285xDOI Listing
January 2015