Bioprospecting of Endophytic Fungi as Promising Anti-MRSA Agents

Wei, Yee-Min,Tan, Joo-Shun,Tang, Hock-Wei,Tong, Woei-Yenn,Leong, Chean-Ring,Tan, Wen-Nee The Korean Society of Pharmacognosy 2022 Natural Product Sciences Vol.28 No.3

Methicillin-resistant Staphylococcus aureus (MRSA) is a serious threat to the global healthcare system. Ineffective and resistance to antibiotic treatments have increased morbidity and mortality rates worldwide. New and effective antibiotics are needed to combat against bacterial resistance. Endophytic fungi are crucial reservoirs of novel bioactive metabolites. In particular, the secondary metabolites show promising therapeutic potential, notably, antibacterial. This review discussed the emerging potential of endophytic fungi as anti-MRSA agents. The ecological sources of endophytic fungi were discussed with the synthesis of bioactive metabolites. The mode of antibacterial actions was elucidated to give a better understanding of the mechanisms involved. This review may serve as an important reference for future discovery and developments of anti-MRSA agents from endophytic fungi.

Endophytic Diaporthe sp. ED2 Produces a Novel Anti-Candidal Ketone Derivative

( Tong Woei Yenn ),( Leong Chean Ring ),( Tan Wen Nee ),( Melati Khairuddean ),( Latiffah Zakaria ),( Darah Ibrahim ) 한국미생물생명공학회(구 한국산업미생물학회) 2017 Journal of microbiology and biotechnology Vol.27 No.6

This study aimed to examine the anti-candidal efficacy of a novel ketone derivative isolated from Diaporthe sp. ED2, an endophytic fungus residing in medicinal herb Orthosiphon stamieus Benth. The ethyl acetate extract of the fungal culture was separated by open column and reverse phase high-performance liquid chromatography (HPLC). The eluent at retention time 5.64 min in the HPLC system was the only compound that exhibited anti-candidal activity on Kirby-Bauer assay. The structure of the compound was also elucidated by nuclear magnetic resonance and spectroscopy techniques. The purified anti-candidal compound was obtained as a colorless solid and characterized as 3-hydroxy-5-methoxyhex-5-ene-2,4-dione. On broth microdilution assay, the compound also exhibited fungicidal activity on a clinical strain of Candida albicans at a minimal inhibitory concentration of 3.1 μg/ml. The killing kinetic analysis also revealed that the compound was fungicidal against C. albicans in a concentration- and time-dependent manner. The compound was heat-stable up to 70°C, but its anti-candidal activity was affected at pH 2.

Garcinexanthone G, a Selective Butyrylcholinesterase Inhibitor from the Stem Bark of Garcinia atroviridis

Kooi-Yeong Khaw,Vikneswaran Murugaiyah,Melati Khairuddean,Wen-Nee Tan 한국생약학회 2018 Natural Product Sciences Vol.24 No.2

The present study was undertaken to investigate the isolated compounds from the stem bark of Garcinia atroviridis as potential cholinesterase inhibitors and the ligand-enzyme interactions of selected bioactive compounds in silico. The in vitro cholinesterase results showed that quercetin (3) was the most active AChE inhibitor (12.65 ? 1.57 ?g/ml) while garcinexanthone G (6) was the most active BChE inhibitor (18.86 ? 2.41 ?g/ml). It is noteworthy to note that compound 6 was a selective inhibitor with the selectivity index of 11.82. Molecular insight from docking interaction further substantiate that orientation of compound 6 in the catalytic site which enhanced its binding affinity as compared to other xanthones. The nature of protein-ligand interactions of compound 6 is mainly hydrogen bonding, and the hydroxyl group of compound 6 at C-10 is vital in BChE inhibition activity. Therefore, compound 6 is a notable lead for further drug design and development of BChE selective inhibitor.

Chemical Composition and Antimicrobial Efficiency of Swietenia macrophylla Seed Extract on Clinical Wound Pathogens

Hanan Kumar Gopalan,Nor Faizzah Md Hanafiah,Leong Chean Ring,Wen-Nee Tan,Suzana Wahidin,Teo Siew Hway,Tong Woei Yenn 한국생약학회 2019 Natural Product Sciences Vol.25 No.1

Microbial wound infection prolonged the hospitalization and increase the cost for wound management. Silver is commonly used as antimicrobial wound dressing. However, it causes several adverse side effects. Hence, this study was aimed to evaluate the antimicrobial efficiency of Swietenia macrophylla seed extract on clinical wound pathogens. Besides, the bioactive constituents of the seed extract were also determined. S. macrophylla seeds were extracted with methanol by maceration method. The seed extract inhibited 5 test bacteria and 1 yeast on disc diffusion assay. The antibacterial activity was broad spectrum, as the extract inhibited both Gram positive and Gram negative bacteria. On kill curve analysis, the antibacterial activity of the seed extract was concentration-dependent, the increase of extract concentration resulted in more reduction of bacterial growth. The extract also caused 99.9% growth reduction of Bacillus subtilis relative to control. A total of 21 compounds were detected in gas chromatography- mass spectrometry analysis. The predominant compounds present in the extract were oleic acid (18.56%) and linoleic acid (17.72%). In conclusion, the methanolic extract of S. macrophylla seeds exhibited significant antimicrobial activity on clinical wound pathogens. Further investigations should be conducted to purify other bioactive compounds from the seeds of S. macrophylla.

Potential of Endophytic Diaporthe sp. as a New Source of Bioactive Compounds

( Kashvintha Nagarajan ),( Woei-yenn Tong ),( Chean-ring Leong ),( Wen-nee Tan ) 한국미생물생명공학회(구 한국산업미생물학회) 2021 Journal of microbiology and biotechnology Vol.31 No.4

Endophytic fungi are symbiotically related to plants and spend most of their life cycle within them. In nature, they have a crucial role in plant micro-ecosystem. They are harnessed for their bioactive compounds to counter human health problems and diseases. Endophytic Diaporthe sp. is a widely distributed fungal genus that has garnered much interest within the scientific community. A substantial number of secondary metabolites have been detected from Diaporthe sp. inhabited in various plants. As such, this minireview highlights the potential of Diaporthe sp. as a rich source of bioactive compounds by emphasizing on their diverse chemical entities and potent biological properties. The bioactive compounds produced are of significant importance to act as new lead compounds for drug discovery and development.

Potential Antimicrobial Applications of Chitosan Nanoparticles (ChNP)

( Nur Amiera Syuhada Rozman ),( Tong Woei Yenn ),( Leong Chean Ring ),( Tan Wen Nee ),( Muhammad Ariff Hasanolbasori ),( Siti Zubaidah Abdullah ) 한국미생물·생명공학회 2019 Journal of microbiology and biotechnology Vol.29 No.7

Polymeric nanoparticles are widely used for drug delivery due to their biodegradability property. Among the wide array of polymers, chitosan has received growing interest among researchers. It was widely used as a vehicle in polymeric nanoparticles for drug targeting. This review explored the current research on the antimicrobial activity of chitosan nanoparticles (ChNP) and the impact on the clinical applications. The antimicrobial activities of ChNP were widely reported against bacteria, fungi, yeasts and algae, in both in vivo and in vitro studies. For pharmaceutical applications, ChNP were used as antimicrobial coating for promoting wound healing, preventing infections and combating the rise of infectious disease. Besides, ChNP also exhibited significant inhibitory activities on foodborne microorganisms, particularly on fruits and vegetables. It is noteworthy that ChNP can be also applied to deliver antimicrobial drugs, which further enhance the efficiency and stability of the antimicrobial agent. The present review addresses the potential antimicrobial applications of ChNP from these few aspects.

Chemical Composition and Antimicrobial Efficacy of Helminthostachys zeylanica against Foodborne Bacillus cereus

Tong Woei Yenn,Leong Chean Ring,Khairul Azly Zahan,Muhammad Sharir Abdul Rahman,Wen-Nee Tan,Bintul Jauza’ Shaik Alaudin 한국생약학회 2018 Natural Product Sciences Vol.24 No.1

Helminthostachys zeylanica is a rare plant grows in lightly shaded areas. The fern was traditionally used as antipyretic and antiphlogistic agents. This study was aimed to evaluate the antibacterial potential of H. zeylanica on foodborne Bacillus cereus. The chemical composition of its ethanolic extract was also determined. The plant samples were collected at Kampung Kebun Relong, Kedah, Malaysia. The ethanolic extract showed significant inhibitory activity on B. cereus with a sizeable clear zone detected on disc diffusion assay. On broth microdilution assay, the MIC of the extract on B. cereus was 6.25 mg/ml and the MBC was 12.5 mg/ml. The inhibitory activity of the extract on B. cereus was bactericidal. In the growth dynamic study, the antibacterial efficacy of the extract was concentration dependent, where a lower colony forming unit count was obtained with increased extract concentration. The SEM micrograph of extract treated B. cereus cells showed invaginations of cell wall. The bacterial cell structure collapsed after 24 h exposure to the extract. The GCMS analysis of the extract showed that the major constituents of the extract were phenol (36.26%) and quercetin (29.70%). This study is important as it shows the potential use of H. zeylanica as an effective agent to control B. cereus related infections.

Antimicrobial efficacy of endophytic Penicillium purpurogenum ED76 against clinical pathogens and its possible mode of action

Yenn, Tong Woei,Ibrahim, Darah,Chang, Lee Kok,Ab Rashid, Syarifah,Ring, Leong Chean,Nee, Tan Wen,Noor, Muhamad Izham bin Muhamad The Microbiological Society of Korea 2017 미생물학회지 Vol.53 No.3

This study was aimed to evaluate the antimicrobial activity of Penicillium purpurogenum ED76 on several clinically important microorganisms. The endophytic fungus P. purpurogenum ED76 was previously isolated from Swietenia macrophylla leaf. The antimicrobial efficacy of P. purpurogenum ED76 dichloromethane extract was determined via disc diffusion and broth microdilution assay. A kill curve study was conducted and the morphology of extract treated bacterial cells were viewed under scanning electron microscope. The dichloromethane extract showed significant inhibitory activity on 4 test bacteria and 2 test yeasts. The minimal inhibitory concentration of the extract ranged from 125 to $1,000{\mu}g/ml$, which indicates the different susceptibility levels of the test microorganisms to the fungal extract. The kill curve study has revealed a concentration-dependent inhibition for all test microorganisms. With the increase of the extract concentration, the microbial growth was significantly reduced. The scanning electron micrograph of dichloromethane extract-treated Staphylococcus aureus cells showed the total damage of the cells. The cell wall invagination of the bacterial cells also indicates the loss of cellular materials and metabolic activity. The gas chromatography mass spectrometry analysis of the extract also showed that the major compound was stigmasterol, which constitutes 45.30% of the total area. The dichloromethane extract of P. purpurogenum ED76 exhibited significant inhibitory activity on several clinically important bacteria and yeasts. The study proposed a possible mode of action that the extract cause significant damage to the morphology of S. aureus cells.

Anthocyanins from Clitoria ternatea Attenuate Food-Borne Penicillium expansum and its Potential Application as Food Biopreservative

Chean-Ring Leong,Muhammad Afif Kamarul Azizi,Md Abu Taher,Suzana Wahidin,Kok-Chang Lee,Wen-Nee Tan,Woei-Yenn Tong 한국생약학회 2017 Natural Product Sciences Vol.23 No.2

Clitoria ternatea or Commonly known blue pea, is a perennial climber crop native to Asian countries. The current study was aimed to evaluate the antimicrobial activity C. ternatea extract on food borne microorganisms and its antifungal effect on Penicillium expansum. The extract showed significant antimicrobial activity against 3 Gram positive bacteria, 2 Gram negative bacteria and 1 filamentous fungus on disc diffusion assay. The extract also showed good biocidal effect on all Gram positive bacteria tested and P. expansum. However, the kill curve analysis revealed that the fungicidal activity of the extract against P. expansum conidia was depend on the concentration of the extract and the time of exposure of the conidia to the extract. The scanning electron micrograph of the extract treated P. expansum culture showed alterations in the morphology of fungal hyphae. The germination of P. expansum conidia was completely inhibited and conidial development was totally suppressed by the extract, suggesting the possible mode of action of anthocyanin. Besides, the extract also exhibited 5.0-log suppression of microbial growth relative to control in the rice model. The results indicate the potential use of the C. ternatea anthocyanin as food biopreservative.

Antimicrobial Efficacy of Penicillium amestolkiae elv609 Extract Treated Cotton Fabric for Diabetic Wound Care

( Nur Amiera Syuhada Binti Rozman ),( Nurhanis Syafiqah Binti Mohd Nor Hamin ),( Leong Chean Ring ),( Tan Wen Nee ),( Mahfuzah Binti Mustapha ),( Tong Woei Yenn ) 한국균학회 2017 Mycobiology Vol.45 No.3

Diabetes mellitus is a chronic disorder which affects millions of population worldwide. Global estimates published in 2010 reported the world diabetic prevalence as 6.4%, affecting 285 million adults. Foot ulceration and wound infection are major forms of disabilities arising from diabetic diseases. This study was aimed to develop a natural antimicrobial finishing on medical grade textile that meets American Association of Textiles Chemists and Colorists (AATCC) standard. The textile samples were finished with the ethanolic extract of Penicillium amestolkiae elv609, an endophytic fungus isolated from Orthosiphon stamineus Benth (common name: cat`s whiskers). Endophyte is defined as microorganism that reside in the living plant tissue, without causing apparent disease symptom to the host. The antimicrobial efficacy of the ethanolic extract of P. minioluteum was tested on clinical pathogens isolated from diabetic wound. The extract exhibited significant inhibitory activity against 4 bacteria and 1 yeast with the minimal inhibitory concentration ranged from 6.25 to 12.5 mg/mL. The results indicate different susceptibility levels of the test microorganism to the ethanolic extract. However, the killing activity of the extract was concentration-dependent. The finished medical textile showed excellent antimicrobial efficacy on AATCC test assays. All the microbial cultures treated with the textile sample displayed a growth reduction of 99.9% on Hoheinstein Challenge Test. The wash durability of the finished textile was found good even after 50 washes with commercial detergent. Besides, the gas chromatography mass spectrometry analysis showed that 6-octadecenoic acid and diethyl phthalate were the main bioactive constituents of the extract. In conclusion, the developed medical textile showed good antimicrobial efficacy on laboratory tests. This work can be extended to in vivo trials for developing healthcare textile products for antimicrobial applications.