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Tzu Shan Ng
Department of Molecular Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur 50603, Malaysia;(N.H.T.);(T.S.N.)

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Communication
Published: 14 February 2019 in Toxins
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The protein abundances of phospholipases A2 in cobra venom proteomes appear to vary among cobra species. To determine the unique distribution of snake venom phospholipases A2 (svPLA2) in the cobras, the svPLA2 activities for 15 cobra species were examined with an acidimetric and a colorimetric assay, using egg yolk suspension and 4-nitro-3-octanoyloxy benzoic acid (NOBA) as the substrate. The colorimetric assay showed significant correlation between svPLA2 enzymatic activities with the svPLA2 protein abundances in venoms. High svPLA2 activities were observed in the venoms of Asiatic spitting cobras (Naja sputatrix, Naja sumatrana) and moderate activities in Asiatic non-spitters (Naja naja, Naja atra, Naja kaouthia), African spitters (subgenus Afronaja), and forest cobra (subgenus Boulengerina). African non-spitting cobras of subgenus Uraeus (Naja haje, Naja annulifera, Naja nivea, Naja senegalensis) showed exceptionally low svPLA2 enzymatic activities. The negligible PLA2 activity in Uraeus cobra venoms implies that PLA2 may not be ubiquitous in all snake venoms. The svPLA2 in cobra envenoming varies depending on the cobra species. This may potentially influence the efficacy of cobra antivenom in specific use for venom neutralization.

ACS Style

Choo Hock Tan; Kin Ying Wong; Nget Hong Tan; Tzu Shan Ng; Kae Yi Tan. Distinctive Distribution of Secretory Phospholipases A2 in the Venoms of Afro-Asian Cobras (Subgenus: Naja, Afronaja, Boulengerina and Uraeus). Toxins 2019, 11, 116 .

AMA Style

Choo Hock Tan, Kin Ying Wong, Nget Hong Tan, Tzu Shan Ng, Kae Yi Tan. Distinctive Distribution of Secretory Phospholipases A2 in the Venoms of Afro-Asian Cobras (Subgenus: Naja, Afronaja, Boulengerina and Uraeus). Toxins. 2019; 11 (2):116.

Chicago/Turabian Style

Choo Hock Tan; Kin Ying Wong; Nget Hong Tan; Tzu Shan Ng; Kae Yi Tan. 2019. "Distinctive Distribution of Secretory Phospholipases A2 in the Venoms of Afro-Asian Cobras (Subgenus: Naja, Afronaja, Boulengerina and Uraeus)." Toxins 11, no. 2: 116.

Journal article
Published: 06 February 2019 in Toxins
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Trimeresurus nebularis is a montane pit viper that causes bites and envenomation to various communities in the central highland region of Malaysia, in particular Cameron’s Highlands. To unravel the venom composition of this species, the venom proteins were digested by trypsin and subjected to nano-liquid chromatography-tandem mass spectrometry (LC-MS/MS) for proteomic profiling. Snake venom metalloproteinases (SVMP) dominated the venom proteome by 48.42% of total venom proteins, with a characteristic distribution of P-III: P-II classes in a ratio of 2:1, while P-I class was undetected. Snaclecs constituted the second most venomous protein family (19.43%), followed by snake venom serine proteases (SVSP, 14.27%), phospholipases A2 (5.40%), disintegrins (5.26%) and minor proteins including cysteine-rich secretory proteins, L-amino acid oxidases, phosphodiesterases, 5′-nucleotidases. The venomic profile correlates with local (painful progressive edema) and systemic (hemorrhage, coagulopathy, thrombocytopenia) manifestation of T. nebularis envenoming. As specific antivenom is unavailable for T. nebularis, the hetero-specific Thai Green Pit viper Monovalent Antivenom (GPVAV) was examined for immunological cross-reactivity. GPVAV exhibited good immunoreactivity to T. nebularis venom and the antivenom effectively cross-neutralized the hemotoxic and lethal effects of T. nebularis (lethality neutralizing potency = 1.6 mg venom per mL antivenom). The findings supported GPVAV use in treating T. nebularis envenoming.

ACS Style

Choo Hock Tan; Kae Yi Tan; Tzu Shan Ng; Evan S.H. Quah; Ahmad Khaldun Ismail; Sumana Khomvilai; Visith Sitprija; Nget Hong Tan. Venomics of Trimeresurus (Popeia) nebularis, the Cameron Highlands Pit Viper from Malaysia: Insights into Venom Proteome, Toxicity and Neutralization of Antivenom. Toxins 2019, 11, 95 .

AMA Style

Choo Hock Tan, Kae Yi Tan, Tzu Shan Ng, Evan S.H. Quah, Ahmad Khaldun Ismail, Sumana Khomvilai, Visith Sitprija, Nget Hong Tan. Venomics of Trimeresurus (Popeia) nebularis, the Cameron Highlands Pit Viper from Malaysia: Insights into Venom Proteome, Toxicity and Neutralization of Antivenom. Toxins. 2019; 11 (2):95.

Chicago/Turabian Style

Choo Hock Tan; Kae Yi Tan; Tzu Shan Ng; Evan S.H. Quah; Ahmad Khaldun Ismail; Sumana Khomvilai; Visith Sitprija; Nget Hong Tan. 2019. "Venomics of Trimeresurus (Popeia) nebularis, the Cameron Highlands Pit Viper from Malaysia: Insights into Venom Proteome, Toxicity and Neutralization of Antivenom." Toxins 11, no. 2: 95.

Journal article
Published: 23 December 2018 in Toxins
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The venom proteome of Hydrophis curtus (synonym: Lapemis hardwickii) from Penang, Malaysia was investigated with nano-electrospray ionization-liquid chromatography tandem mass spectrometry (ESI-LCMS/MS) of the reverse-phase high-performance liquid chromatography (HPLC) venom fractions. Thirty distinct protein forms were identified as toxins from ten families. The three major protein families were phospholipase A2 (PLA2, 62.0% of total venom proteins), three-finger toxin (3FTX, 26.33%) and cysteine-rich secretory protein (CRiSP, 9.00%). PLA2 comprises diverse homologues (11 forms), predominantly the acidic subtypes (48.26%). 3FTX composed of one short alpha-neurotoxin (SNTX, 22.89%) and four long alpha-neurotoxins (LNTX, 3.44%). Both SNTX and LNTX were lethal in mice (intravenous LD50 = 0.10 and 0.24 μg/g, respectively) but the PLA2 were non-lethal (LD50 >1 μg/g). The more abundant and toxic SNTX appeared to be the main driver of venom lethality (holovenom LD50 = 0.20 μg/g). The heterologous Sea Snake Antivenom (SSAV, Australia) effectively cross-neutralized the venom (normalized potency = 9.35 mg venom neutralized per g antivenom) and the two neurotoxins in vivo, with the LNTX being neutralized more effectively (normalized potency = 3.5 mg toxin/g antivenom) than SNTX (normalized potency = 1.57 mg/g). SSAV immunorecognition was strong toward PLA2 but moderate-to-weak toward the alpha-neurotoxins, indicating that neutralization of the alpha-neurotoxins should be further improved.

ACS Style

Choo Hock Tan; Kae Yi Tan; Tzu Shan Ng; Si Mui Sim; Nget Hong Tan. Venom Proteome of Spine-Bellied Sea Snake (Hydrophis curtus) from Penang, Malaysia: Toxicity Correlation, Immunoprofiling and Cross-Neutralization by Sea Snake Antivenom. Toxins 2018, 11, 3 .

AMA Style

Choo Hock Tan, Kae Yi Tan, Tzu Shan Ng, Si Mui Sim, Nget Hong Tan. Venom Proteome of Spine-Bellied Sea Snake (Hydrophis curtus) from Penang, Malaysia: Toxicity Correlation, Immunoprofiling and Cross-Neutralization by Sea Snake Antivenom. Toxins. 2018; 11 (1):3.

Chicago/Turabian Style

Choo Hock Tan; Kae Yi Tan; Tzu Shan Ng; Si Mui Sim; Nget Hong Tan. 2018. "Venom Proteome of Spine-Bellied Sea Snake (Hydrophis curtus) from Penang, Malaysia: Toxicity Correlation, Immunoprofiling and Cross-Neutralization by Sea Snake Antivenom." Toxins 11, no. 1: 3.

Journal article
Published: 06 October 2018 in Journal of Herbmed Pharmacology
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ACS Style

Tzu Shan Ng; Ley Juen Looi; Ban Shui Ong; Pei Pei Chong. Antifungal and anti-biofilm effects of shallot (Allium ascalonicum) aqueous extract on Candida albicans. Journal of Herbmed Pharmacology 2018, 7, 236 -242.

AMA Style

Tzu Shan Ng, Ley Juen Looi, Ban Shui Ong, Pei Pei Chong. Antifungal and anti-biofilm effects of shallot (Allium ascalonicum) aqueous extract on Candida albicans. Journal of Herbmed Pharmacology. 2018; 7 (4):236-242.

Chicago/Turabian Style

Tzu Shan Ng; Ley Juen Looi; Ban Shui Ong; Pei Pei Chong. 2018. "Antifungal and anti-biofilm effects of shallot (Allium ascalonicum) aqueous extract on Candida albicans." Journal of Herbmed Pharmacology 7, no. 4: 236-242.

Journal article
Published: 01 June 2016 in Infection, Genetics and Evolution
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Glucose is an important fuel source to support many living organisms. Its importance in the physiological fitness and pathogenicity of Candida glabrata, an emerging human fungal pathogen has not been extensively studied. The present study aimed to investigate the effects of glucose on the growth, biofilm formation, antifungal susceptibility and oxidative stress resistance of C. glabrata. In addition, its effect on the expression of a putative high affinity glucose sensor gene, SNF3 was also investigated. Glucose concentrations were found to exert effects on the physiological responses of C. glabrata. The growth rate of the species correlated positively to the amount of glucose. In addition, low glucose environments were found to induce C. glabrata to form biofilm and resist amphotericin B. Conversely, high glucose environments promoted oxidative stress resistance of C. glabrata. The expression of CgSNF3 was found to be significantly up-regulated in low glucose environments. The expression of SNF3 gene in clinical isolates was found to be higher compared to ATCC laboratory strains in low glucose concentrations, which may explain the better survivability of clinical isolates in the low glucose environment. These observations demonstrated the impact of glucose in directing the physiology and virulence fitness of C. glabrata through the possible modulation by SNF3 as a glucose sensor, which in turn aids the species to adapt, survive and thrive in hostile host environment.

ACS Style

Tzu Shan Ng; Mohd Nasir Mohd Desa; Doblin Sandai; Pei Pei Chong; Leslie Thian Lung Than. Growth, biofilm formation, antifungal susceptibility and oxidative stress resistance of Candida glabrata are affected by different glucose concentrations. Infection, Genetics and Evolution 2016, 40, 331 -338.

AMA Style

Tzu Shan Ng, Mohd Nasir Mohd Desa, Doblin Sandai, Pei Pei Chong, Leslie Thian Lung Than. Growth, biofilm formation, antifungal susceptibility and oxidative stress resistance of Candida glabrata are affected by different glucose concentrations. Infection, Genetics and Evolution. 2016; 40 ():331-338.

Chicago/Turabian Style

Tzu Shan Ng; Mohd Nasir Mohd Desa; Doblin Sandai; Pei Pei Chong; Leslie Thian Lung Than. 2016. "Growth, biofilm formation, antifungal susceptibility and oxidative stress resistance of Candida glabrata are affected by different glucose concentrations." Infection, Genetics and Evolution 40, no. : 331-338.

Original research article
Published: 01 December 2015 in Frontiers in Microbiology
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Candida glabrata is an emerging human fungal pathogen that has efficacious nutrient sensing and responsiveness ability. It can be seen through its ability to thrive in diverse range of nutrient limited-human anatomical sites. Therefore, nutrient sensing particularly glucose sensing is thought to be crucial in contributing to the development and fitness of the pathogen. This study aimed to elucidate the role of SNF3 (Sucrose Non Fermenting 3) as a glucose sensor and its possible role in contributing to the fitness and survivability of C. glabrata in glucose-limited environment. The SNF3 knockout strain was constructed and subjected to different glucose concentrations to evaluate its growth, biofilm formation, amphotericin B susceptibility, ex vivo survivability and effects on the transcriptional profiling of the sugar receptor repressor (SRR) pathway-related genes. The SNF3Δ strain showed a retarded growth in low glucose environments (0.01% and 0.1%) in both fermentation and respiration-preferred conditions but grew well in high glucose concentration environments (1% and 2%). It was also found to be more susceptible to amphotericin B in low glucose environment (0.1%) and macrophage engulfment but showed no difference in the biofilm formation capability. The deletion of SNF3 also resulted in the down-regulation of about half of hexose transporters genes (4 out of 9). Overall, the deletion of SNF3 causes significant reduction in the ability of C. glabrata to sense limited surrounding glucose and consequently disrupts its competency to transport and perform the uptake of this critical nutrient. This study highlighted the role of SNF3 as a high affinity glucose sensor and its role in aiding the survivability of C. glabrata particularly in glucose limited environment.

ACS Style

Tzu Shan Ng; Shu Yih Chew; Premmala Rangasamy; Mohd Nasir Mohd Desa; Doblin Sandai; Pei Pei Chong; Leslie Thian Lung Than. SNF3 as High Affinity Glucose Sensor and Its Function in Supporting the Viability of Candida glabrata under Glucose-Limited Environment. Frontiers in Microbiology 2015, 6, 1334 .

AMA Style

Tzu Shan Ng, Shu Yih Chew, Premmala Rangasamy, Mohd Nasir Mohd Desa, Doblin Sandai, Pei Pei Chong, Leslie Thian Lung Than. SNF3 as High Affinity Glucose Sensor and Its Function in Supporting the Viability of Candida glabrata under Glucose-Limited Environment. Frontiers in Microbiology. 2015; 6 ():1334.

Chicago/Turabian Style

Tzu Shan Ng; Shu Yih Chew; Premmala Rangasamy; Mohd Nasir Mohd Desa; Doblin Sandai; Pei Pei Chong; Leslie Thian Lung Than. 2015. "SNF3 as High Affinity Glucose Sensor and Its Function in Supporting the Viability of Candida glabrata under Glucose-Limited Environment." Frontiers in Microbiology 6, no. : 1334.

Journal article
Published: 21 November 2015 in Jundishapur Journal of Microbiology
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Background: The sensing mechanism of glucose in Saccharomyces cerevisiae is well studied. However, such information is scarcely found in other yeast species such as Candida glabrata. Objectives: This study aimed to identify the glucose sensing pathway related genes of C. glabrata and to analyze the regulation pattern of these genes in response to different surrounding glucose concentrations through the quantitative real time polymerase chain reaction (qRT-PCR). Materials and Methods: Phylogenetic analysis was carried out on predicted amino acid sequences of C. glabrata and S. cerevisiae to compare their degree of similarity. In addition, the growth of C. glabrata in response to different amounts of glucose (0%, 0.01%, 0.1%, 1% and 2%) was evaluated via the spot dilution assay on prepared agar medium. Besides, the SNF3 and RGT2, which act as putative glucose sensors, and the RGT1 and MIG1, which act as putative transcriptional regulators and selected downstream hexose transporters (HXTs), were analysed through qRT-PCR analysis for the gene expression level under different glucose concentrations. Results: Comparative analysis of predicted amino acids in the phylogenetic tree showed high similarity between C. glabrata and S cerevisiae. Besides, C. glabrata demonstrated the capability to grow in glucose levels as low as 0.01% in the spot dilution assay. In qRT-PCR analysis, differential expressions were observed in selected genes when C. glabrata was subjected to different glucose concentrations. Conclusions: The constructed phylogenetic tree suggests the close evolutionary relationship between C. glabrata and S. cerevisiae. The capability of C. glabrata to grow in extremely low glucose environments and the differential expression of selected glucose-sensing related genes suggested the possible role of these genes in modulating the growth of C. glabrata in response to different glucose concentrations. This study helps deepen our understanding of the glucose sensing mechanism in C. glabrata and serves to provide fundamental data that may assist in unveiling this mechanism as a potential drug target. Keywords: Glucose Transport Proteins; Facilitative; Phylogeny; Candida glabrata

ACS Style

Tzu Shan Ng; Mohd Nasir Mohd Desa; Doblin Sandai; Pei Pei Chong; Leslie Thian Lung Than. Phylogenetic and Transcripts Profiling of Glucose Sensing Related Genes in Candida glabrata. Jundishapur Journal of Microbiology 2015, 8, 1 .

AMA Style

Tzu Shan Ng, Mohd Nasir Mohd Desa, Doblin Sandai, Pei Pei Chong, Leslie Thian Lung Than. Phylogenetic and Transcripts Profiling of Glucose Sensing Related Genes in Candida glabrata. Jundishapur Journal of Microbiology. 2015; 8 (11):1.

Chicago/Turabian Style

Tzu Shan Ng; Mohd Nasir Mohd Desa; Doblin Sandai; Pei Pei Chong; Leslie Thian Lung Than. 2015. "Phylogenetic and Transcripts Profiling of Glucose Sensing Related Genes in Candida glabrata." Jundishapur Journal of Microbiology 8, no. 11: 1.