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Fulltext Cell-based influenza vaccine: current production, halal status assessment, and recommendations towards Islamic-compliant manufacturing

Zulkarnain NN, Anuar N, Abd Rahman N, Sheikh Abdullah SR, Alias MN, Yaacob M, et al.

Hum Vaccin Immunother, 2021 07 03;17(7):2158-2168.
PMID: 33539195 DOI: 10.1080/21645515.2020.1865044

Influenza virus is a life-threatening pathogen that infects millions of people every year, with annual mortality in the hundreds of thousands. The scenario for controlling infection has worsened with increasing numbers of vaccine hesitancy cases reported worldwide due to objections on safety, religious and other grounds. Uses of haram (impermissible) and mashbooh (doubtful) ingredients in vaccine production has raised doubts among Muslim consumers and consequently stimulated serious vaccine hesitancy. To address this major problem, we have reviewed and recommended some alternatives appropriate for manufacturing cell-based influenza vaccine which comply with Islamic laws and consumers' needs. Intensive assessments of current influenza vaccine production in both scientific and Islamic views have led to the identification of four main ingredients deemed impermissible in novel sharia-compliant (approved by Islamic laws) vaccine manufacturing. Only some of these impermissible components could be replaced with halal (permissible) alternatives, while others remain impermissible due to unavailability and unsuitability.
Mutation detection in GJB2 gene among Malays with non-syndromic hearing loss

Zainal SA, Md Daud MK, Abd Rahman N, Zainuddin Z, Alwi Z

Int J Pediatr Otorhinolaryngol, 2012 Aug;76(8):1175-9.
PMID: 22613756 DOI: 10.1016/j.ijporl.2012.04.027

To identify the mutations in the GJB2 gene and to determine its association with non-syndromic hearing loss in Malays.
Food waste and food processing waste for biohydrogen production: a review

Yasin NH, Mumtaz T, Hassan MA, Abd Rahman N

J Environ Manage, 2013 Nov 30;130:375-85.
PMID: 24121591 DOI: 10.1016/j.jenvman.2013.09.009

Food waste and food processing wastes which are abundant in nature and rich in carbon content can be attractive renewable substrates for sustainable biohydrogen production due to wide economic prospects in industries. Many studies utilizing common food wastes such as dining hall or restaurant waste and wastes generated from food processing industries have shown good percentages of hydrogen in gas composition, production yield and rate. The carbon composition in food waste also plays a crucial role in determining high biohydrogen yield. Physicochemical factors such as pre-treatment to seed culture, pH, temperature (mesophilic/thermophilic) and etc. are also important to ensure the dominance of hydrogen-producing bacteria in dark fermentation. This review demonstrates the potential of food waste and food processing waste for biohydrogen production and provides a brief overview of several physicochemical factors that affect biohydrogen production in dark fermentation. The economic viability of biohydrogen production from food waste is also discussed.
Fulltext 3-(2-Amino-phenyl-sulfanyl)-1,3-diphenyl-propan-1-one

Yaeghoobi M, Khaledi H, Abdullah Z, Abd Rahman N

Acta Crystallogr Sect E Struct Rep Online, 2011 Jul 1;67(Pt 7):o1693.
PMID: 21837090 DOI: 10.1107/S1600536811022112

In the title compound, C(21)H(19)NOS, the three aromatic rings are not coplanar, the dihedral angles between them being 84.75 (7), 88.01 (8) and 8.36 (16)°. In the crystal, two types of C-H⋯ π inter-actions, one of which is weak, and N-H⋯π inter-actions link the mol-ecules into layers parallel to the ab plane.
Fulltext Evaluation of the current bacteriological profile and antibiotic sensitivity pattern in chronic suppurative otitis media

Wan Draman WNA, Md Daud MK, Mohamad H, Hassan SA, Abd Rahman N

Laryngoscope Investig Otolaryngol, 2021 Dec;6(6):1300-1306.
PMID: 34938866 DOI: 10.1002/lio2.682

OBJECTIVE: To determine the current microbiological profile of chronic suppurative otitis media (CSOM), their antimicrobial sensitivity, their resistance pattern to locally available antibiotics and the appropriate antibiotic against isolated microorganisms causing CSOM.
METHODS: This cross-sectional study involved 91 ear swab specimens obtained from patients clinically diagnosed with active CSOM. Swabs were cultured for microbial identification according to a standard protocol. We performed antibiotic susceptibility testing, using the modified Kirby-Bauer disc diffusion method, and the diameter of the inhibition zone was interpreted based Clinical Laboratory Standards Institute guidelines.
RESULTS: Microbial growth was seen in 85 (93.4%) samples, but 6 (6.6%) samples had no growth. Among the samples with growth, 63 (69.2%) were monomicrobial, 13 (14.3%) were polymicrobial, and 9 (9.9%) were of mixed growth with more than three microorganisms. The most common bacteria isolated was Pseudomonas aeruginosa (32.6%) followed by Staphylococcus aureus (16.9%) and Klebsiella spp. (5.6%). The most sensitive antibiotics against P aeruginosa were ceftazidime, meropenem, piperacillin-tazobactam, and cefepime. S aureus showed the highest sensitivity toward rifampin, cefoxitin, and fusidic acid.
CONCLUSIONS: The bacteriological profile of CSOM showed a high prevalence of P aeruginosa, followed by S aureus and Klebsiella spp. with different distributions in different age groups. We observed a declining pattern of their antibiotic sensitivity. It is important to be aware of the current trend of the bacteriological profiles and to revise the antibiotic regime according to both the sensitivity and age groups.Level of Evidence: NA.
Fulltext Synthesis, Biological Evaluation and Molecular Modelling of 2'-Hydroxychalcones as Acetylcholinesterase Inhibitors

Sukumaran SD, Chee CF, Viswanathan G, Buckle MJ, Othman R, Abd Rahman N, et al.

Molecules, 2016 Jul 22;21(7).
PMID: 27455222 DOI: 10.3390/molecules21070955

A series of 2'-hydroxy- and 2'-hydroxy-4',6'-dimethoxychalcones was synthesised and evaluated as inhibitors of human acetylcholinesterase (AChE). The majority of the compounds were found to show some activity, with the most active compounds having IC50 values of 40-85 µM. Higher activities were generally observed for compounds with methoxy substituents in the A ring and halogen substituents in the B ring. Kinetic studies on the most active compounds showed that they act as mixed-type inhibitors, in agreement with the results of molecular modelling studies, which suggested that they interact with residues in the peripheral anionic site and the gorge region of AChE.
Myofibroblastoma of the breast

Shanmugasiva VV, Ramli Hamid MT, Fadzli F, Shaleen Kaur KS, Abd Rahman N, Rahmat K

Malays J Pathol, 2018 Dec;40(3):349-353.
PMID: 30580368

INTRODUCTION: Myofibroblastoma is a rare benign mesenchymal tumour arising from the stromal elements of the breast tissue. Histopathological variants such as classic, cellular, collagenous / fibrous, lipomatous, infiltrative, myxoid and epithelioid have been identified. Most myofibroblastomas are immunoreactive for CD34, actin, CD10 and desmin, usually express oestrogen receptor (ER), progesterone receptor (PR) and variably express androgen receptor (AR).
CASE REPORT: We report a case of myofibroblastoma in an octogenarian male presenting with painless solitary breast lump. Mammography (digital tomosynthesis) and ultrasound showed a well-circumscribed hyperdense mass and hypoechoic, solid, oval mass with peripheral vascularity respectively. Patient underwent wide local excision.
DISCUSSION: Diverse characteristics of myofibroblastoma on imaging necessitates histopathological analysis for an accurate diagnosis. Myofibroblastoma are often confused with fibroadenomas due to the benign imaging characteristics and with malignant neoplasia due to their wide morphological spectrum. Surgical excision is considered curative.
Fulltext Fusion of protegrin-1 and plectasin to MAP30 shows significant inhibition activity against dengue virus replication

Rothan HA, Bahrani H, Mohamed Z, Abd Rahman N, Yusof R

PLoS One, 2014;9(4):e94561.
PMID: 24722532 DOI: 10.1371/journal.pone.0094561

Dengue virus (DENV) broadly disseminates in tropical and sub-tropical countries and there are no vaccine or anti-dengue drugs available. DENV outbreaks cause serious economic burden due to infection complications that requires special medical care and hospitalization. This study presents a new strategy for inexpensive production of anti-DENV peptide-fusion protein to prevent and/or treat DENV infection. Antiviral cationic peptides protegrin-1 (PG1) and plectasin (PLSN) were fused with MAP30 protein to produce recombinant antiviral peptide-fusion protein (PG1-MAP30-PLSN) as inclusion bodies in E. coli. High yield production of PG1-MAP30-PLSN protein was achieved by solubilization of inclusion bodies in alkaline buffer followed by the application of appropriate refolding techniques. Antiviral PG1-MAP30-PLSN protein considerably inhibited DENV protease (NS2B-NS3pro) with half-maximal inhibitory concentration (IC50) 0.5±0.1 μM. The real-time proliferation assay (RTCA) and the end-point proliferation assay (MTT assay) showed that the maximal-nontoxic dose of the peptide-fusion protein against Vero cells is approximately 0.67±0.2 μM. The cell-based assays showed considerable inhibition of the peptide-fusion protein against binding and proliferating stages of DENV2 into the target cells. The peptide-fusion protein protected DENV2-challeged mice with 100% of survival at the dose of 50 mg/kg. In conclusion, producing recombinant antiviral peptide-fusion protein by combining short antiviral peptide with a central protein owning similar activity could be useful to minimize the overall cost of short peptide production and take advantage of its synergistic antiviral activities.
Fulltext Estimation of soil erodibility in Peninsular Malaysia: A case study using multiple linear regression and artificial neural networks

Rehman MA, Abd Rahman N, Ibrahim ANH, Kamal NA, Ahmad A

Heliyon, 2024 Apr 15;10(7):e28854.
PMID: 38576554 DOI: 10.1016/j.heliyon.2024.e28854

Soil erodibility (K) is an essential component in estimating soil loss indicating the soil's susceptibility to detach and transport. Data Computing and processing methods, such as artificial neural networks (ANNs) and multiple linear regression (MLR), have proven to be helpful in the development of predictive models for natural hazards. The present case study aims to assess the efficiency of MLR and ANN models to forecast soil erodibility in Peninsular Malaysia. A total of 103 samples were collected from various sites and K values were calculated using the Tew equation developed for Malaysian soil. From several extracted parameters, the outcomes of correlation and principal component analysis (PCA) revealed the influencing factors to be used in the development of ANN and MLR models. Based on the correlation and PCA results, two sets of influencing factors were employed to develop predictive models. Two MLR (MLR-1 and MLR-2) models and four neural networks (NN-1, NN-2, NN-3, and NN-4) optimized using Levenberg-Marquardt (LM) and scaled conjugate gradient (SCG) were developed and evaluated. The model performance validation was conducted using the coefficient of determination (R2), mean squared error (MSE), root mean squared error (RMSE), and Nash-Sutcliffe efficiency coefficient (NSE). The analysis showed that ANN models outperformed MLR models. The R2 values of 0.446 (MLR-1), 0.430 (MLR-2), 0.894 (NN-1), 0.855 (NN-2), 0.940 (NN-3), and 0.826 (NN-4); MSE values of 0.0000306 (MLR-1), 0.0000315 (MLR-2), 0.0000158 (NN-1), 0.0000261 (NN-2), 0.0000318 (NN-3), and 0.0000216 (NN-4) suggested the higher accuracy and lower modelling error of ANN models as compared with MLR. This study could provide an empirical basis and methodological support for K factor estimation in the region.
Fulltext A heuristic ranking approach on capacity benefit margin determination using Pareto-based evolutionary programming technique

Othman MM, Abd Rahman N, Musirin I, Fotuhi-Firuzabad M, Rajabi-Ghahnavieh A

ScientificWorldJournal, 2015;2015:731013.
PMID: 25879068 DOI: 10.1155/2015/731013

This paper introduces a novel multiobjective approach for capacity benefit margin (CBM) assessment taking into account tie-line reliability of interconnected systems. CBM is the imperative information utilized as a reference by the load-serving entities (LSE) to estimate a certain margin of transfer capability so that a reliable access to generation through interconnected system could be attained. A new Pareto-based evolutionary programming (EP) technique is used to perform a simultaneous determination of CBM for all areas of the interconnected system. The selection of CBM at the Pareto optimal front is proposed to be performed by referring to a heuristic ranking index that takes into account system loss of load expectation (LOLE) in various conditions. Eventually, the power transfer based available transfer capability (ATC) is determined by considering the firm and nonfirm transfers of CBM. A comprehensive set of numerical studies are conducted on the modified IEEE-RTS79 and the performance of the proposed method is numerically investigated in detail. The main advantage of the proposed technique is in terms of flexibility offered to an independent system operator in selecting an appropriate solution of CBM simultaneously for all areas.
Fulltext Thymoquinone loaded in nanostructured lipid carrier showed enhanced anticancer activity in 4T1 tumor-bearing mice

Ong YS, Saiful Yazan L, Ng WK, Abdullah R, Mustapha NM, Sapuan S, et al.

Nanomedicine (Lond), 2018 07;13(13):1567-1582.
PMID: 30028248 DOI: 10.2217/nnm-2017-0322

AIM: To investigate the enhancement of anticancer activity of thymoquinone (TQ) by the use of nanostructured lipid carrier (NLC) in 4T1 tumor-bearing female BALB/c mice.
MATERIAL & METHODS: TQ was incorporated into NLC (TQNLC) by using high pressure homogenization. TQNLC and TQ were orally administered to the mice.
RESULTS & CONCLUSION: TQNLC and TQ are potential chemotherapeutic drugs as they exhibited anticancer activity. The use of NLC as a carrier has enhanced the therapeutic property of TQ by increasing the survival rate of mice. The antimetastasis effect of TQNLC and TQ to the lungs was evidence by downregulation of MMP-2. TQNLC and TQ induced apoptosis via modulation of Bcl-2 and caspase-8 in the intrinsic apoptotic pathway.
Association between dietary 3-monochloropropane-1,2-diol esters (3-MCPDE) and renal cancer in Peninsular Malaysia: exposure assessment and matched case-control study

Muhamad Rosli SH, Lau MS, Khalid T, Maarof SK, Jeyabalan S, Sirdar Ali S, et al.

Food Addit Contam Part A Chem Anal Control Expo Risk Assess, 2023 Apr;40(4):475-492.
PMID: 36947708 DOI: 10.1080/19440049.2023.2183068

3-Monochloropropane-1,2-diol esters (3-MCPDE) are food contaminants commonly found in refined vegetable oils and fats, which have possible carcinogenic implications in humans. To investigate this clinically, we conducted an occurrence level analysis on eight categories of retail and cooked food commonly consumed in Malaysia. This was used to estimate the daily exposure level, through a questionnaire-based case-control study involving 77 subjects with renal cancer, with 80 matching controls. Adjusted Odds Ratio (AOR) was calculated using the multiple logistic regression model adjusted for confounding factors. A pooled estimate of total 3-MCPDE intake per day was compared between both groups, to assess exposure and disease outcome. Among the food categories analysed, vegetable fats and oils recorded the highest occurrence levels (mean: 1.91 ± 1.90 mg/kg), significantly more than all other food categories (p
Fulltext Extended high frequency hearing loss in tinnitus-positive chronic suppurative otitis media patient

Mohd Salehuddin NS, Md Daud MK, Nik Othman NA, Abd Rahman N

Laryngoscope Investig Otolaryngol, 2021 Oct;6(5):1137-1141.
PMID: 34667858 DOI: 10.1002/lio2.651

Objectives: To determine the association between extended high frequency hearing loss and tinnitus in normal cochlear function based on a conventional audiometry chronic suppurative otitis media (CSOM) patient.
Design and methods: A cross-sectional study was conducted on 220 ears diagnosed as having CSOM with an equal number of tinnitus and without tinnitus groups. Only those with normal cochlear function based on conventional pure tone audiometry (250 Hz to 8 kHz) were included. They were further tested for hearing at extended high frequencies of up to 16 kHz. The severity of tinnitus was tested using a tinnitus questionnaire.
Results: The prevalence of extended high frequency hearing loss in the normal cochlear function CSOM patients with tinnitus was 81.8% (95% CI 74.5%, 89.1%), whereas the prevalence in the tinnitus negative group was 30.0% (95% CI 21.3%, 38.7%). There was a significant association between extended high frequency hearing loss and tinnitus in CSOM patients (P
Fulltext Halocarbon emissions by selected tropical seaweeds: species-specific and compound-specific responses under changing pH

Mithoo-Singh PK, Keng FS, Phang SM, Leedham Elvidge EC, Sturges WT, Malin G, et al.

PeerJ, 2017;5:e2918.
PMID: 28149690 DOI: 10.7717/peerj.2918

Five tropical seaweeds, Kappaphycus alvarezii (Doty) Doty ex P.C. Silva, Padina australis Hauck, Sargassum binderi Sonder ex J. Agardh (syn. S. aquifolium (Turner) C. Agardh), Sargassum siliquosum J. Agardh and Turbinaria conoides (J. Agardh) Kützing, were incubated in seawater of pH 8.0, 7.8 (ambient), 7.6, 7.4 and 7.2, to study the effects of changing seawater pH on halocarbon emissions. Eight halocarbon species known to be emitted by seaweeds were investigated: bromoform (CHBr3), dibro-momethane (CH2Br2), iodomethane (CH3I), diiodomethane (CH2I2), bromoiodomethane (CH2BrI), bromochlorometh-ane (CH2BrCl), bromodichloromethane (CHBrCl2), and dibro-mochloromethane (CHBr2Cl). These very short-lived halocarbon gases are believed to contribute to stratospheric halogen concentrations if released in the tropics. It was observed that the seaweeds emit all eight halocarbons assayed, with the exception of K. alvarezii and S. binderi for CH2I2 and CH3I respectively, which were not measurable at the achievable limit of detection. The effect of pH on halocarbon emission by the seaweeds was shown to be species-specific and compound specific. The highest percentage changes in emissions for the halocarbons of interest were observed at the lower pH levels of 7.2 and 7.4 especially in Padina australis and Sargassum spp., showing that lower seawater pH causes elevated emissions of some halocarbon compounds. In general the seaweed least affected by pH change in terms of types of halocarbon emission, was P. australis. The commercially farmed seaweed K. alvarezii was very sensitive to pH change as shown by the high increases in most of the compounds in all pH levels relative to ambient. In terms of percentage decrease in maximum quantum yield of photosynthesis (Fv∕Fm) prior to and after incubation, there were no significant correlations with the various pH levels tested for all seaweeds. The correlation between percentage decrease in the maximum quantum yield of photosynthesis (Fv∕Fm) and halocarbon emission rates, was significant only for CH2BrCl emission by P. australis (r = 0.47; p ≤ 0.04), implying that photosynthesis may not be closely linked to halocarbon emissions by the seaweeds studied. Bromine was the largest contributor to the total mass of halogen emitted for all the seaweeds at all pH. The highest total amount of bromine emitted by K. alvarezii (an average of 98% of total mass of halogens) and the increase in the total amount of chlorine with decreasing seawater pH fuels concern for the expanding seaweed farming activities in the ASEAN region.
Gender differences in coping skills of parents with hearing-impaired children

Md Daud MK, Noor SS, Yusoff MN, Abd Rahman N, Zakaria MN

B-ENT, 2013;9(4):319-23.
PMID: 24597108

To assess differences between the coping strategies of the mothers and fathers with hearing-impaired children.
Fulltext Determining food safety in canned food using fuzzy logic based on sulphur dioxide, benzoic acid and sorbic acid concentration

Mavani NR, Mohd Ali J, Hussain MA, Abd Rahman N, Hashim H

Heliyon, 2024 Feb 29;10(4):e26273.
PMID: 38384537 DOI: 10.1016/j.heliyon.2024.e26273

Canned food market demand has arisen due to the higher need for instant and ready-to-eat food. Food preservatives are often added to canned and processed foods to prolong their shelf life and help to sustain the quality, taste, color, and food texture. However, excessive usage of such food preservatives can lead to various diseases and health issues including palpitations, allergies, and cancer. Therefore, food preservative detection in food samples is essential for safe consumption and health well-being. This paper proposed a fuzzy logic framework to determine the safety of food products based on the concentration of sulphur dioxide (SD), benzoic acid (BA), and sorbic acid (SA) in five different food categories as referred to the Food Acts 1983 and Food Regulations 1985 in Malaysia. The fuzzy logic framework comprises of Mamdani inference system design with 90 fuzzy rules, 15 and 5 membership functions for both the input and output parameters respectively. 50 random values and 10 lab analysis results based on the industrial samples were used to validate the developed algorithms in ensuring the safety of the food products. The membership functions generated for the three inputs (SD, BA, and SA) during the fuzzification steps are based on the maximum allowable limit from the food acts. The defuzzification of fuzzy logic gave an average output value of 0.1565, 0.1350, 0.1150, 0.1100, and 0.1550 for chicken curry with potatoes, satay sauce, sardine in tomato sauce, anchovies paste, and sardine spread accordingly. Results obtained from the fuzzy logic framework concluded that all the industrial samples are safe to be eaten and comply with the Sixth Schedule, Regulation 20 in both Acts.
Chalcones with electron-withdrawing and electron-donating substituents: anticancer activity against TRAIL resistant cancer cells, structure-activity relationship analysis and regulation of apoptotic proteins

Mai CW, Yaeghoobi M, Abd-Rahman N, Kang YB, Pichika MR

Eur J Med Chem, 2014 Apr 22;77:378-87.
PMID: 24675137 DOI: 10.1016/j.ejmech.2014.03.002

In the present study, a series of 46 chalcones were synthesised and evaluated for antiproliferative activities against the human TRAIL-resistant breast (MCF-7, MDA-MB-231), cervical (HeLa), ovarian (Caov-3), lung (A549), liver (HepG2), colorectal (HT-29), nasopharyngeal (CNE-1), erythromyeloblastoid (K-562) and T-lymphoblastoid (CEM-SS) cancer cells. The chalcone 38 containing an amino (-NH2) group on ring A was the most potent and selective against cancer cells. The effects of the chalcone 38 on regulation of 43 apoptosis-related markers in HT-29 cells were determined. The results showed that 20 apoptotic markers (Bad, Bax, Bcl-2, Bcl-w, Bid, Bim, CD40, Fas, HSP27, IGF-1, IGFBP-4, IGFBP-5, Livin, p21, Survivin, sTNF-R2, TRAIL-R2, XIAP, caspase-3 and caspase-8) were either up regulated or down regulated.
Effect of irradiance on the emission of short-lived halocarbons from three common tropical marine microalgae

Lim YK, Keng FS, Phang SM, Sturges WT, Malin G, Abd Rahman N

PeerJ, 2019;7:e6758.
PMID: 31041152 DOI: 10.7717/peerj.6758

Marine algae have been reported as important sources of biogenic volatile halocarbons that are emitted into the atmosphere. These compounds are linked to destruction of the ozone layer, thus contributing to climate change. There may be mutual interactions between the halocarbon emission and the environment. In this study, the effect of irradiance on the emission of halocarbons from selected microalgae was investigated. Using controlled laboratory experiments, three tropical marine microalgae cultures, Synechococcus sp. UMACC 371 (cyanophyte), Parachlorella sp. UMACC 245 (chlorophyte) and Amphora sp. UMACC 370 (diatom) were exposed to irradiance of 0, 40 and 120 µmol photons m-2s-1. Stress in the microalgal cultures was indicated by the photosynthetic performance (Fv/Fm, maximum quantum yield). An increase in halocarbon emissions was observed at 120 µmol photons m-2s-1, together with a decrease in Fv/Fm. This was most evident in the release of CH3I by Amphora sp. Synechococcus sp. was observed to be the most affected by irradiance as shown by the increase in emissions of most halocarbons except for CHBr3 and CHBr2Cl. High positive correlation between Fv/Fm and halocarbon emission rates was observed in Synechococcus sp. for CH2Br2. No clear trends in correlation could be observed for the other halocarbons in the other two microalgal species. This suggests that other mechanisms like mitochondria respiration may contribute to halocarbon production, in addition to photosynthetic performance.
Fulltext Discovery of potential anti-infectives against Staphylococcus aureus using a Caenorhabditis elegans infection model

Kong C, Yehye WA, Abd Rahman N, Tan MW, Nathan S

BMC Complement Altern Med, 2014;14:4.
PMID: 24393217 DOI: 10.1186/1472-6882-14-4

The limited antibiotic options for effective control of methicillin-resistant Staphylococcus aureus infections has led to calls for new therapeutic approaches to combat this human pathogen. An alternative approach to control MRSA is through the use of anti-infective agents that selectively disrupt virulence-mediated pathways without affecting microbial cell viability or by modulating the host natural immune defenses to combat the pathogen.
Fulltext Suppression of Staphylococcus aureus biofilm formation and virulence by a benzimidazole derivative, UM-C162

Kong C, Chee CF, Richter K, Thomas N, Abd Rahman N, Nathan S

Sci Rep, 2018 02 09;8(1):2758.
PMID: 29426873 DOI: 10.1038/s41598-018-21141-2

Staphylococcus aureus is a major cause of nosocomial infections and secretes a diverse spectrum of virulence determinants as well as forms biofilm. The emergence of antibiotic-resistant S. aureus highlights the need for alternative forms of therapeutics other than conventional antibiotics. One route to meet this need is screening small molecule derivatives for potential anti-infective activity. Using a previously optimized C. elegans - S. aureus small molecule screen, we identified a benzimidazole derivative, UM-C162, which rescued nematodes from a S. aureus infection. UM-C162 prevented the formation of biofilm in a dose-dependent manner without interfering with bacterial viability. To examine the effect of UM-C162 on the expression of S. aureus virulence genes, a genome-wide transcriptome analysis was performed on UM-C162-treated pathogen. Our data indicated that the genes associated with biofilm formation, particularly those involved in bacterial attachment, were suppressed in UM-C162-treated bacteria. Additionally, a set of genes encoding vital S. aureus virulence factors were also down-regulated in the presence of UM-C162. Further biochemical analysis validated that UM-C162-mediated disruption of S. aureus hemolysins, proteases and clumping factors production. Collectively, our findings propose that UM-C162 is a promising compound that can be further developed as an anti-virulence agent to control S. aureus infections.

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