Publications by authors named "Hui-Min Neoh"

41 Publications

Methicillin-Resistant (MRSA) Clonal Replacement in a Malaysian Teaching Hospital: Findings from an Eight-Year Interval Molecular Surveillance.

Antibiotics (Basel) 2021 Mar 19;10(3). Epub 2021 Mar 19.

UKM Medical Molecular Biology Institute (UMBI), Universiti Kebangsaan Malaysia, Kuala Lumpur 56000, Malaysia.

Periodical surveillance on nosocomial pathogens is important for antimicrobial stewardship and infection control. The first methicillin-resistant (MRSA) molecular surveillance in Hospital Canselor Tuanku Muhriz (HCTM), a Malaysian teaching hospital, was performed in 2009. The dominant clone was identified as an MRSA carrying SCC type III-SCC with and + toxin genes. In this study, we report the findings of the second HCTM MRSA surveillance carried out in 2017, after an interval of 8 years. Antibiotic susceptibility testing, SCC, toxin gene, and typing were performed for 222 MRSA strains isolated in 2017. Most strains were resistant to ciprofloxacin, erythromycin, clindamycin, cefoxitin, and penicillin ( = 126, 56.8%), belong to SCC type IV ( = 205, 92.3%), type t032 ( = 160, 72.1%) and harboured + toxin genes ( = 172, 77.5%). There was significant association between resistance of the aforementioned antibiotics with SCC type IV ( < 0.05), t032 ( < 0.001), and + carriage ( < 0.05). Results from this second MRSA surveillance revealed the occurrence of clonal replacement in HCTM during an interval of not more than 8 years. Investigation of the corresponding phenotype changes in this new dominant MRSA clone is currently on-going.
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http://dx.doi.org/10.3390/antibiotics10030320DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8003425PMC
March 2021

Parvimonas micra, Peptostreptococcus stomatis, Fusobacterium nucleatum and Akkermansia muciniphila as a four-bacteria biomarker panel of colorectal cancer.

Sci Rep 2021 Feb 3;11(1):2925. Epub 2021 Feb 3.

UKM Medical Molecular Biology Institute (UMBI), UKM Medical Centre, Universiti Kebangsaan Malaysia, Jalan Yaa'cob Latiff, Bandar Tun Razak, Cheras, 56000, Kuala Lumpur, Malaysia.

Dysbiosis of the gut microbiome has been associated with the pathogenesis of colorectal cancer (CRC). We profiled the microbiome of gut mucosal tissues from 18 CRC patients and 18 non-CRC controls of the UKM Medical Centre (UKMMC), Kuala Lumpur, Malaysia. The results were then validated using a species-specific quantitative PCR in 40 CRC and 20 non-CRC tissues samples from the UMBI-UKMMC Biobank. Parvimonas micra, Fusobacterium nucleatum, Peptostreptococcus stomatis and Akkermansia muciniphila were found to be over-represented in our CRC patients compared to non-CRC controls. These four bacteria markers distinguished CRC from controls (AUROC = 0.925) in our validation cohort. We identified bacteria species significantly associated (cut-off value of > 5 fold abundance) with various CRC demographics such as ethnicity, gender and CRC staging; however, due to small sample size of the discovery cohort, these results could not be further verified in our validation cohort. In summary, Parvimonas micra, Fusobacterium nucleatum, Peptostreptococcus stomatis and Akkermansia muciniphila were enriched in our local CRC patients. Nevertheless, the roles of these bacteria in CRC initiation and progression remains to be investigated.
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http://dx.doi.org/10.1038/s41598-021-82465-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7859180PMC
February 2021

The heterogeneic distribution of Helicobacter pylori cag pathogenicity island reflects different pathologies in multiracial Malaysian population.

Braz J Infect Dis 2020 Nov - Dec;24(6):545-551. Epub 2020 Nov 4.

University of Aberdeen, School of Medicine, Medical Sciences and Nutrition Aberdeen, Dept. of Medical Microbiology, United Kingdom.

Background: Helicobacter pylori harbouring cag-pathogenicity island (cagPAI) which encodes type IV secretion system (T4SS) and cagA virulence gene are involved in inflammation of the gastric mucosa. We examined all the 27 cagPAI genes in 88 H. pylori isolates from patients of different ethnicities and examined the association of the intactness of cagPAI region with histopathological scores of the gastric mucosa.

Results: 96.6% (n=85) of H. pylori isolates were cagPAI-positive with 22.4% (19/85) having an intact cagPAI, whereas 77.6% (66/85) had a partial/rearranged cagPAI. The frequency of cag2 and cag14 were found to be significantly higher in H. pylori isolated from Malays, whereas cag4 was predominantly found in Chinese isolates. The cag24 was significantly found in higher proportions in Malay and Indian isolates than in Chinese isolates. The intactness of cagPAI region showed an association with histopathological scores of the gastric mucosa. Significant association was observed between H. pylori harbouring partial cagPAI with higher density of bacteria and neutrophil activity, whereas strains lacking cagPAI were associated with higher inflammatory score.

Conclusions: The genotypes of H. pylori strains with various cagPAI rearrangement associated with patients' ethnicities and histopathological scores might contribute to the pathogenesis of H. pylori infection in a multi-ethnic population.
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http://dx.doi.org/10.1016/j.bjid.2020.10.005DOI Listing
December 2020

Advantages and Limitations of 16S rRNA Next-Generation Sequencing for Pathogen Identification in the Diagnostic Microbiology Laboratory: Perspectives from a Middle-Income Country.

Diagnostics (Basel) 2020 Oct 14;10(10). Epub 2020 Oct 14.

BioEasy Sdn. Bhd., Selangor 40170, Malaysia.

Bacterial culture and biochemical testing (CBtest) have been the cornerstone of pathogen identification in the diagnostic microbiology laboratory. With the advent of Sanger sequencing and later, next-generation sequencing, 16S rRNA next-generation sequencing (16SNGS) has been proposed to be a plausible platform for this purpose. Nevertheless, usage of the 16SNGS platform has both advantages and limitations. In addition, transition from the traditional methods of CBtest to 16SNGS requires procurement of costly equipment, timely and sustainable maintenance of these platforms, specific facility infrastructure and technical expertise. All these factors pose a challenge for middle-income countries, more so for countries in the lower middle-income range. In this review, we describe the basis for CBtest and 16SNGS, and discuss the limitations, challenges, advantages and future potential of using 16SNGS for bacterial pathogen identification in diagnostic microbiology laboratories of middle-income countries.
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http://dx.doi.org/10.3390/diagnostics10100816DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7602188PMC
October 2020

Dengue epidemic in Malaysia: urban versus rural comparison of dengue immunoglobulin G seroprevalence among Malaysian adults aged 35-74 years.

Trans R Soc Trop Med Hyg 2020 11;114(11):798-811

UKM Medical Molecular Biology Institute, Universiti Kebangsaan Malaysia, Kuala Lumpur, 56000, Malaysia.

Background: A periodic serosurvey of dengue seroprevalence is vital to determine the prevalence of dengue in countries where this disease is endemic. This study aimed to determine the prevalence of dengue immunoglobulin G (IgG) seropositivity among healthy Malaysian adults living in urban and rural areas.

Methods: A total of 2598 serum samples (1417 urban samples, 1181 rural samples) were randomly collected from adults ages 35-74 y. The presence of the dengue IgG antibody and neutralising antibodies to dengue virus (DENV) 1-4 was determined using enzyme-linked immunosorbent assay and the plaque reduction neutralisation test assay, respectively.

Results: The prevalence of dengue IgG seropositivity was 85.39% in urban areas and 83.48% in rural areas. The seropositivity increased with every 10-y increase in age. Ethnicity was associated with dengue seropositivity in urban areas but not in rural areas. The factors associated with dengue seropositivity were sex and working outdoors. In dengue IgG-positive serum samples, 98.39% of the samples had neutralising antibodies against DENV3, but only 70.97% of them had neutralising antibodies against DENV4.

Conclusion: The high seroprevalence of dengue found in urban and rural areas suggests that both urban and rural communities are vital for establishing and sustaining DENV transmission in Malaysia.
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http://dx.doi.org/10.1093/trstmh/traa056DOI Listing
November 2020

Molecular surveillance of methicillin-susceptible (MSSA) isolated over a one-year period from a Malaysian Teaching Hospital.

Germs 2020 Jun 2;10(2):104-111. Epub 2020 Jun 2.

PhD, UKM Medical Molecular Biology Institute (UMBI), Universiti Kebangsaan Malaysia, Cheras, 56000 Kuala Lumpur, Malaysia.

Introduction: We report the results of a molecular surveillance study carried out on methicillin-susceptible (MSSA) isolated in a one-year duration from Hospital Canselor Tuanku Muhriz (HCTM), a tertiary hospital located in Kuala Lumpur, Malaysia.

Methods: The first strain isolated from each MSSA infection in HCTM during the year 2009 was included into the study. Antimicrobial susceptibility testing and agr group typing were carried out for all strains; virulence gene (, , TSST-1 and PVL) typing results of the strains were obtained from a previous study. Pulsed-field gel electrophoresis (PFGE) was done on selected strains from the orthopedic ward. Relationship(s) between different typing methods used in the study was investigated, where a p value of <0.05 indicated significant association between typing methods.

Results: A total of 880 MSSA strains were included into the study. The strains were generally susceptible to most antibiotics, with most of them carrying and -I (51.6%, n=454; 39.8%, n=350, respectively). A total of 17 PFGE pulsotypes were identified using an 80% similarity cut-off value, where the main pulsotype (pulsotype E) consisted of 24 isolates (23.5%). -III strains were found to be usually positive for both and (p<0.05). In addition, some PFGE pulsotypes were also characteristic of certain virulence genes or groups.

Conclusions: We did not identify a dominant MSSA clone circulating in HCTM in 2009. Nevertheless, results from this molecular surveillance will provide good baseline data for the hospital's second surveillance planned for the year 2020.
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http://dx.doi.org/10.18683/germs.2020.1191DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7330523PMC
June 2020

Pulsed-field gel electrophoresis (PFGE): A review of the "gold standard" for bacteria typing and current alternatives.

Infect Genet Evol 2019 10 22;74:103935. Epub 2019 Jun 22.

Department of Emergency Medicine, Faculty of Medicine, Universiti Kebangsaan Malaysia, Malaysia.

Pulsed-field gel electrophoresis (PFGE) is considered the "gold standard" for bacteria typing. The method involves enzyme restriction of bacteria DNA, separation of the restricted DNA bands using a pulsed-field electrophoresis chamber, followed by clonal assignment of bacteria based on PFGE banding patterns. Various PFGE protocols have been developed for typing different bacteria, leading it to be one of the most widely used methods for phylogenetic studies, food safety surveillance, infection control and outbreak investigations. On the other hand, as PFGE is lengthy and labourious, several PCR-based typing methods can be used as alternatives for research purposes. Recently, matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF MS) and whole genome sequencing (WGS) have also been proposed for bacteria typing. In fact, as WGS provides more information, such as antimicrobial resistance and virulence of the tested bacteria in comparison to PFGE, more and more laboratories are currently transitioning from PFGE to WGS for bacteria typing. Nevertheless, PFGE will remain an affordable and relevant technique for small laboratories and hospitals in years to come.
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http://dx.doi.org/10.1016/j.meegid.2019.103935DOI Listing
October 2019

Oxidative stress resistance and fitness-compensatory response in vancomycin-intermediate (VISA).

Can J Microbiol 2019 Aug 7;65(8):623-628. Epub 2019 May 7.

a UKM Medical Molecular Biology Institute (UMBI), Universiti Kebangsaan Malaysia, Malaysia.

In this study, vancomycin-intermediate (VISA) cells carrying and (or) mutations were shown to be more resistant to oxidative stress. infected with these strains in turn demonstrated lower survival. Altered regulation in oxidative stress response and virulence appear to be physiological adaptations associated with the VISA phenotype in the Mu50 lineage.
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http://dx.doi.org/10.1139/cjm-2019-0048DOI Listing
August 2019

Establishment of an immunofluorescence assay to detect IgM antibodies to Nipah virus using HeLa cells expressing recombinant nucleoprotein.

J Virol Methods 2019 07 5;269:83-87. Epub 2019 Apr 5.

Department of Veterinary Science, National Institute of Infectious Diseases, 1-23-1 Toyama, Shinjuku, Tokyo, 162-8640, Japan.

A novel indirect fluorescent antibody test (IFAT) for detection of IgM against Nipah virus (NiV) was developed using HeLa 229 cells expressing recombinant NiV nucleocapsid protein (NiV-N). The NiV IFAT was evaluated using three panels of sera: a) experimentally produced sera from NiV-N-immunized/pre-immunized macaques, b) post-infection human sera associated with a Nipah disease outbreak in the Philippines in 2014, and c) human sera from a non-exposed Malaysian population. Immunized macaque sera showed a characteristic granular staining pattern of the NiV-N expressed antigen in HeLa 229 cells, which was readily distinguished from negative-binding results of the pre-immunized macaque sera. The IgM antibody titers in sequential serum samples (n = 7) obtained from three Nipah patients correlated well with previously published results using conventional IgM capture ELISA and SNT serology. The 90 human serum samples from unexposed persons were unreactive by IFAT. The IFAT utilizing NiV-N-expressing HeLa 229 cells to detect IgM antibody in an early stage of NiV infection is an effective approach, which could be utilized readily in local laboratories to complement other capabilities in NiV-affected countries.
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http://dx.doi.org/10.1016/j.jviromet.2019.03.009DOI Listing
July 2019

Rapid Detection of Sepsis using CESDA: the Caenorhabditis elegans Sepsis Detection Assay.

Rev Soc Bras Med Trop 2019 Mar 14;52:e20180300. Epub 2019 Mar 14.

UKM Medical Molecular Biology Institute (UMBI), Universiti Kebangsaan Malaysia, Malaysia.

Introduction: The nematode Caenorhabditis elegans was used as a biological sensor to detect the urine of sepsis patients (CESDA assay).

Methods: C. elegans was aliquoted onto the center of assay plates and allowed to migrate towards sepsis (T) or control (C) urine samples spotted on the same plate. The number of worms found in either (T) or (C) was scored at 10-minute intervals over a 60-minute period.

Results: The worms were able to identify the urine (<48 hours) of sepsis patients rapidly within 20 minutes (AUROC=0.67, p=0.012) and infection within 40 minutes (AUROC=0.80, p=0.016).

Conclusions: CESDA could be further explored for sepsis diagnosis.
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http://dx.doi.org/10.1590/0037-8682-0300-2018DOI Listing
March 2019

Analyzing the Secretome of Gut Microbiota as the Next Strategy For Early Detection of Colorectal Cancer.

Proteomics 2019 05 25;19(10):e1800176. Epub 2019 Jan 25.

UKM Medical Molecular Biology Institute, Universiti Kebangsaan Malaysia, 56000 Cheras, Kuala Lumpur, Malaysia.

Dysbiosis of gut microbiome can contribute to inflammation, and subsequently initiation and progression of colorectal cancer (CRC). Throughout these stages, various proteins and metabolites are secreted to the external environment by microorganisms or the hosts themselves. Studying these proteins may help enhance our understanding of the host-microorganism relationship or they may even serve as useful biomarkers for CRC. However, secretomic studies of gut microbiome of CRC patients, until now, are scarcely performed. In this review article, the focus is on the roles of gut microbiome in CRC, the current findings on CRC secretome are highlighted, and the emerging challenges and strategies to drive forward this area of research are addressed.
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http://dx.doi.org/10.1002/pmic.201800176DOI Listing
May 2019

Comparison of Prognostic Accuracy of the quick Sepsis-Related Organ Failure Assessment between Short- & Long-term Mortality in Patients Presenting Outside of the Intensive Care Unit - A Systematic Review & Meta-analysis.

Sci Rep 2018 11 12;8(1):16698. Epub 2018 Nov 12.

UKM Medical Molecular Biology Institute (UMBI), Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia.

The purpose of this meta-analysis was to compare the ability of the qSOFA in predicting short- (≤30 days or in-hospital mortality) and long-term (>30 days) mortality among patients outside the intensive care unit setting. Studies reporting on the qSOFA and mortality were searched using MEDLINE and SCOPUS. Studies were included if they involved patients presenting to the ED with suspected infection and usage of qSOFA score for mortality prognostication. Data on qSOFA scores and mortality rates were extracted from 36 studies. The overall pooled sensitivity and specificity for the qSOFA were 48% and 86% for short-term mortality and 32% and 92% for long-term mortality, respectively. Studies reporting on short-term mortality were heterogeneous (Odd ratio, OR = 5.6; 95% CI = 4.6-6.8; Higgins's I = 94%), while long-term mortality studies were homogenous (OR = 4.7; 95% CI = 3.5-6.1; Higgins's I = 0%). There was no publication bias for short-term mortality analysis. The qSOFA score showed poor sensitivity but moderate specificity for both short and long-term mortality, with similar performance in predicting both short- and long- term mortality. Geographical region was shown to have nominal significant (p = 0.05) influence on qSOFA short-term mortality prediction.
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http://dx.doi.org/10.1038/s41598-018-35144-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6232181PMC
November 2018

Identification of in the guts of healthy individuals and patients with colorectal cancer: preliminary evidence from a gut microbiome secretome study.

Gut Pathog 2018 10;10:29. Epub 2018 Jul 10.

1UKM Medical Molecular Biology Institute, Universiti Kebangsaan Malaysia, Cheras, Kuala Lumpur, Malaysia.

Over the years, genetic profiling of the gut microbiome of patients with colorectal cancer (CRC) using genome sequencing has suggested over-representation of several bacterial taxa. However, little is known about the protein or metabolite secretions from the microbiota that could lead to CRC pathology. Proteomic studies on the role of microbial secretome in CRC are relatively rare. Here, we report the identification of proteins from found in the stool samples of both healthy individuals and patients with CRC. We found that distinctive sets of proteins were present exclusively and in high intensities in each group. Our finding may trigger a new interest in the role of gut mycobiota in carcinogenesis.
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http://dx.doi.org/10.1186/s13099-018-0258-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6040075PMC
July 2018

16S rRNA Gene Sequencing for Deciphering the Colorectal Cancer Gut Microbiome: Current Protocols and Workflows.

Front Microbiol 2018 27;9:767. Epub 2018 Apr 27.

UKM Medical Molecular Biology Institute, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia.

The human gut holds the densest microbiome ecosystem essential in maintaining a healthy host physiology, whereby disruption of this ecosystem has been linked to the development of colorectal cancer (CRC). The advent of next-generation sequencing technologies such as the 16S rRNA gene sequencing has enabled characterization of the CRC gut microbiome architecture in an affordable and culture-free approach. Nevertheless, the lack of standardization in handling and storage of biospecimens, nucleic acid extraction, 16S rRNA gene primer selection, length, and depth of sequencing and bioinformatics analyses have contributed to discrepancies found in various published studies of this field. Accurate characterization of the CRC microbiome found in different stages of CRC has the potential to be developed into a screening tool in the clinical setting. This mini review aims to concisely compile all available CRC microbiome studies performed till end of 2016 and to suggest standardized protocols that are crucial in developing a gut microbiome screening panel for CRC.
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http://dx.doi.org/10.3389/fmicb.2018.00767DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5934490PMC
April 2018

Effects of simulated microgravity on gene expression and biological phenotypes of a single generation Caenorhabditis elegans cultured on 2 different media.

Life Sci Space Res (Amst) 2017 Nov 24;15:11-17. Epub 2017 Jun 24.

UKM Medical Molecular Biology Institute, Universiti Kebangsaan Malaysia, Malaysia. Electronic address:

Studies of multigenerational Caenorhabditis elegans exposed to long-term spaceflight have revealed expression changes of genes involved in longevity, DNA repair, and locomotion. However, results from spaceflight experiments are difficult to reproduce as space missions are costly and opportunities are rather limited for researchers. In addition, multigenerational cultures of C. elegans used in previous studies contribute to mixture of gene expression profiles from both larvae and adult worms, which were recently reported to be different. Usage of different culture media during microgravity simulation experiments might also give rise to differences in the gene expression and biological phenotypes of the worms. In this study, we investigated the effects of simulated microgravity on the gene expression and biological phenotype profiles of a single generation of C. elegans worms cultured on 2 different culture media. A desktop Random Positioning Machine (RPM) was used to simulate microgravity on the worms for approximately 52 to 54 h. Gene expression profile was analysed using the Affymetrix GeneChip® C. elegans 1.0 ST Array. Only one gene (R01H2.2) was found to be downregulated in nematode growth medium (NGM)-cultured worms exposed to simulated microgravity. On the other hand, eight genes were differentially expressed for C. elegans Maintenance Medium (CeMM)-cultured worms in microgravity; six were upregulated, while two were downregulated. Five of the upregulated genes (C07E3.15, C34H3.21, C32D5.16, F35H8.9 and C34F11.17) encode non-coding RNAs. In terms of biological phenotype, we observed that microgravity-simulated worms experienced minimal changes in terms of lifespan, locomotion and reproductive capabilities in comparison with the ground controls. Taking it all together, simulated microgravity on a single generation of C. elegans did not confer major changes to their gene expression and biological phenotype. Nevertheless, exposure of the worms to microgravity lead to higher expression of non-coding RNA genes, which may play an epigenetic role in the worms during longer terms of microgravity exposure.
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http://dx.doi.org/10.1016/j.lssr.2017.06.002DOI Listing
November 2017

Simplified protocol of gel-based multiple locus variable number of tandem repeats analysis (MLVA) for typing.

Germs 2017 Jun 1;7(2):98-100. Epub 2017 Jun 1.

MD, PhD, UKM Medical Molecular Biology Institute (UMBI), Universiti Kebangsaan Malaysia, Pusat Perubatan UKM, Jalan Yaacob Latiff, Cheras, 56000 Kuala Lumpur, Malaysia.

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http://dx.doi.org/10.18683/germs.2017.1114DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5466828PMC
June 2017

Metaproteomic analysis of human gut microbiota: where are we heading?

J Biomed Sci 2017 Jun 12;24(1):36. Epub 2017 Jun 12.

UKM Medical Molecular Biology Institute (UMBI), Universiti Kebangsaan Malaysia, 56000, Cheras, Kuala Lumpur, Malaysia.

The human gut is home to complex microbial populations that change dynamically in response to various internal and external stimuli. The gut microbiota provides numerous functional benefits that are crucial for human health but in the setting of a disturbed equilibrium, the microbial community can cause deleterious outcomes such as diseases and cancers. Characterization of the functional activities of human gut microbiota is fundamental to understand their roles in human health and disease. Metaproteomics, which refers to the study of the entire protein collection of the microbial community in a given sample is an emerging area of research that provides informative details concerning functional aspects of the microbiota. In this mini review, we present a summary of the progress of metaproteomic analysis for studying the functional role of gut microbiota. This is followed by an overview of the experimental approaches focusing on fecal specimen for metaproteomics and is concluded by a discussion on the challenges and future directions of metaproteomic research.
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http://dx.doi.org/10.1186/s12929-017-0342-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5469034PMC
June 2017

Activated ADI pathway: the initiator of intermediate vancomycin resistance in Staphylococcus aureus.

Can J Microbiol 2017 Mar 19;63(3):260-264. Epub 2016 Oct 19.

a UKM Medical Molecular Biology Institute (UMBI), Universiti Kebangsaan Malaysia, Malaysia.

Comparative proteomic profiling between 2 vancomycin-intermediate Staphylococcus aureus (VISA) strains, Mu50Ω-vraSm and Mu50Ω-vraSm-graRm, and vancomycin-susceptible S. aureus (VSSA) strain Mu50Ω revealed upregulated levels of catabolic ornithine carbamoyltransferase (ArcB) of the arginine catabolism pathway in VISA strains. Subsequent analyses showed that the VISA strains have higher levels of cellular ATP and ammonia, which are by-products of arginine catabolism, and displayed thicker cell walls. We postulate that elevated cytoplasmic ammonia and ATP molecules, resulting from activated arginine catabolism upon acquisition of vraS and graR mutations, are important requirements facilitating cell wall biosynthesis, thereby contributing to thickened cell wall and consequently reduced vancomycin susceptibility in VISA strains.
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http://dx.doi.org/10.1139/cjm-2016-0439DOI Listing
March 2017

Antimicrobial resistance profiling and molecular typing of methicillin-resistant Staphylococcus aureus isolated from a Malaysian teaching hospital.

J Med Microbiol 2016 Dec 7;65(12):1476-1481. Epub 2016 Nov 7.

Department of Medical Microbiology & Immunology, Faculty of Medicine, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia.

The annual prevalence of methicillin-resistant Staphylococcus aureus (MRSA) in Malaysia has been estimated to be 30 % to 40 % of all S. aureus infections. Nevertheless, data on the antimicrobial resistance and genetic diversity of Malaysian MRSAs remain few. In 2009, we collected 318 MRSA strains from various wards of our teaching hospital located in Kuala Lumpur, the capital city of Malaysia, and performed antimicrobial susceptibility testing on these strains. The strains were then molecularly characterized via staphylococcal cassette chromosome (SCC) mec and virulence gene (cna, sea, seb, sec, sed, see, seg, seh, sei, eta, etb, Panton-Valentine leukocidin and toxic shock syndrome toxin-1) typing; a subset of 49 strains isolated from the intensive care unit was also typed using PFGE. Most strains were found to be resistant to ciprofloxacin (92.5 %), erythromycin (93.4 %) and gentamicin (86.8 %). The majority (72.0 %) of strains were found to harbour SCCmec type III-SCCmercury with the presence of ccrC, and carried the sea+cna gene combination (49.3 %), with cna as the most prevalent virulence gene (94.0 %) detected. We identified four PFGE clusters, with pulsotype C (n=19) as the dominant example in the intensive care unit, where this pulsotype was found to be associated with carriage of SCCmec type III and the sea gene (P=0.05 and P=0.02, respectively). In summary, the dominant MRSA circulating in our hospital in 2009 was a clone that was ciprofloxacin, erythromycin and gentamicin resistant, carried SCCmec type III-SCCmercury with ccrC and also harboured the sea+cna virulence genes. This clone also appears to be the dominant MRSA circulating in major hospitals in Kuala Lumpur.
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http://dx.doi.org/10.1099/jmm.0.000387DOI Listing
December 2016

Targeting Staphylococcus aureus Toxins: A Potential form of Anti-Virulence Therapy.

Toxins (Basel) 2016 Mar 15;8(3). Epub 2016 Mar 15.

School of Biosciences and Biotechnology, Faculty of Science and Technology, Universiti Kebangsaan Malaysia, 43600 Bangi, Selangor Darul Ehsan, Malaysia.

Staphylococcus aureus is an opportunistic pathogen and the leading cause of a wide range of severe clinical infections. The range of diseases reflects the diversity of virulence factors produced by this pathogen. To establish an infection in the host, S. aureus expresses an inclusive set of virulence factors such as toxins, enzymes, adhesins, and other surface proteins that allow the pathogen to survive under extreme conditions and are essential for the bacteria's ability to spread through tissues. Expression and secretion of this array of toxins and enzymes are tightly controlled by a number of regulatory systems. S. aureus is also notorious for its ability to resist the arsenal of currently available antibiotics and dissemination of various multidrug-resistant S. aureus clones limits therapeutic options for a S. aureus infection. Recently, the development of anti-virulence therapeutics that neutralize S. aureus toxins or block the pathways that regulate toxin production has shown potential in thwarting the bacteria's acquisition of antibiotic resistance. In this review, we provide insights into the regulation of S. aureus toxin production and potential anti-virulence strategies that target S. aureus toxins.
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http://dx.doi.org/10.3390/toxins8030072DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4810217PMC
March 2016

Seropositivity of dengue antibodies during pregnancy.

ScientificWorldJournal 2014 22;2014:436975. Epub 2014 Dec 22.

Department of Obstetrics & Gynaecology, Medical Faculty, Universiti Kebangsaan Malaysia, Jalan Yaacob Latiff, 56000 Cheras, Kuala Lumpur, Malaysia.

Purpose: Malaysia a dengue endemic country with dengue infections in pregnancy on the rise. The present study was aimed at determining dengue seroprevalence (IgG or IgM) during pregnancy and its neonatal transmission in dengue seropositive women.

Methods: Maternal with paired cord blood samples were tested for dengue antibodies (IgG and IgM) using an enzyme-linked immunosorbent assay (ELISA). Maternal age, parity, occupation, ethnic group, and gestational age were recorded. Data on neonatal Apgar score and admissions to the Neonatal Intensive Care Unit (NICU) were analyzed.

Results: Out of 358 women recruited, about 128 (35.8%) patients were seropositive. Twelve patients (3.4%) had recent infections (IgM positive) and another 116 women (32.4%) were with past infections (IgG positive). All babies born to seropositive mothers had positive IgG paired cord blood; however, no IgM seropositivity was observed. All neonates had good Apgar scores and did not require NICU admission.

Conclusion: In this study, 35.8% pregnant women were found to be dengue seropositive. However, transplacental transfer of IgG antibodies had no detrimental effect on the neonatal outcomes.
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http://dx.doi.org/10.1155/2014/436975DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4283258PMC
September 2015

First report on the molecular epidemiology of Malaysian Staphylococcus epidermidis isolated from a university teaching hospital.

BMC Res Notes 2014 Sep 3;7:597. Epub 2014 Sep 3.

Department of Medical Microbiology and Immunology, Faculty of Medicine, Universiti Kebangsaan Malaysia Medical Molecular Biology Institute (UMBI), UKM Medical Centre, Bandar Tun Razak, Cheras, Kuala Lumpur 56000, Malaysia.

Background: Staphylococcus epidermidis is a pathogen associated with nosocomial infections whose medical importance has increased due to progressively invasive medical procedures. In this study, we characterized the molecular epidemiology of S. epidermidis strains circulating in our university hospital situated in Kuala Lumpur, Malaysia.

Findings: A total of 798 S. epidermidis were isolated from our university hospital, where 56.3% of the isolates were found to be cefoxitin (methicillin) resistant and also positive for the mecA gene. Staphylococcus Cassette Chromosome mec (SCCmec) typing revealed that 39.6% of the methicillin-resistant S. epidermidis (MRSE) were SCCmec-untypeable, with 54.6% harboring the cassette chromosome recombinase C (ccrC) gene. A total of 67 isolates from the neonatal intensive care unit (NICU) was selected for pulsed-field gel electrophoresis (PFGE) typing, where 13 pulsotypes were identified at a cut-off value of 80% similarity. No significant association was found between the PFGE pulsotypes, SCCmec types and antibiotic susceptibilities. Polymerase chain reaction (PCR) assays to detect biofilm-associated genes in the ica operon and also 4 staphylococcal toxin genes (cna, seh, PVL genes and tst-1) revealed that only 8.0% isolates had the complete operon, while cna was the most prevalent toxin gene detected amongst the isolates (35.8%).

Conclusion: To our knowledge, this is the first report on the molecular epidemiology of Malaysian S. epidermidis. We found the strains to be low in virulence potential; nevertheless further studies have to be conducted to determine if this phenomenon translates into a better clinical outcome for patients.
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http://dx.doi.org/10.1186/1756-0500-7-597DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4161766PMC
September 2014

Spatial analysis of colorectal cancer cases in Kuala Lumpur.

Asian Pac J Cancer Prev 2014 ;15(3):1149-54

Department of Community Health, Faculty of Medicine, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia E-mail :

Background: In Malaysia, data from the Malaysian Health Ministry showed colorectal cancer (CRC) to be the second most common type of cancer in 2007-2009, after breast cancer. The same was apparent after looking at males and females cases separately. In the present study, the Geographic Information System (GIS) was employed to describe the distribution of CRC cases in Kuala Lumpur (KL), Malaysia, according to socio-demographic factors (age, gender, ethnicity and district).

Materials And Methods: This retrospective review concerned data for patients diagnosed with colorectal cancer in the years 1995 to 2011 collected from the Wilayah Persekutuan Health Office, taken from the cancer notification form (NCR-2), and patient medical records from the Surgical Department, Universiti Kebangsaan Malaysia Medical Centre (UKMMC). A total of 146 cases were analyzed. All the data collected were analysed using ArcGIS version 10.0 and SPSS version 19.0.

Results: Patients aged 60 to 69 years accounted for the highest proportion of cases (34.2%) and males slightly predominated 76 (52.1%), Chinese had the highest number of registered cases at 108 (74.0%) and staging revealed most cases in the 3rd and 4th stages. Kernel density analysis showed more cases are concentrated up in the northern area of Petaling and Kuala Lumpur subdistricts. Spatial global pattern analysis by average nearest neighbour resulted in nearest neighbour ratio of 0.75, with Z-score of -5.59, p value of <0.01 and the z-score of -5.59. Spatial autocorrelation (Moran's I) showed clustering significant with p<0.01, Z score 3.14 and Moran's Index of 0.007. When mapping clusters with hotspot analysis (Getis-Ord Gi), hot and cold spots were identified. Hot spot areas fell on the northeast side of KL.

Conclusions: This study demonstrated significant spatial patterns of cancer incidence in KL. Knowledge about these spatial patterns can provide useful information to policymakers in the planning of screening of CRC in the targeted population and improvement of healthcare facilities to provide better treatment for CRC patients.
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http://dx.doi.org/10.7314/apjcp.2014.15.3.1149DOI Listing
November 2014

Epidemiological Study on Staphylococcus aureus Isolates Reveals Inverse Relationship between Antibiotic Resistance and Virulence Repertoire.

Indian J Microbiol 2013 Sep 22;53(3):321-2. Epub 2013 Jan 22.

Department of Medical Microbiology and Immunology, Faculty of Medicine, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia.

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http://dx.doi.org/10.1007/s12088-013-0357-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3689395PMC
September 2013

Clonal distribution and possible microevolution of methicillin-resistant Staphylococcus aureus strains in a teaching hospital in Malaysia.

Asian Pac J Trop Biomed 2013 Mar;3(3):224-8

Department of Biomedical Science, Faculty of Allied Health Sciences, Malaysia.

Objective: To genotypically characterize methicillin-resistant Staphylococcus aureus (MRSA) strains isolated from medical and surgical wards in Universiti Kebangsaan Malaysia Medical Centre (UKMMC) in 2009.

Methods: MRSA strains were collected and molecularly typed by pulsed-field gel electrophoresis (PFGE).

Results: PFGE typing on 180 MRSA isolated in UKMMC identified 5 pulsotypes (A-E) and 6 singletons, where pulsotypes B and C were suspected to be divergent clones originating from a single ancestor. This study also showed that most MRSA strains were isolated from swab (119 isolates), followed by blood (22 isolates), tracheal aspirate (11 isolates) and sputum (10 isolates). On the other hand, urine and bone isolates were less, which were 4 and 1 isolates, respectively. The distribution of different pulsotypes of MRSA among wards suggested that MRSA was communicated in surgical and medical wards in UKMMC, with pulsotype B MRSA as the dominant strain. Besides, it was found that most deceased patients were infected by pulsotype B MRSA, however, no particular pulsotype could be associated with patient age, underlying disease, or ward of admittance.

Conclusions: Five pulsotypes of MRSA and 6 singletons were identified, with pulsotype B MRSA as the endemic strains circulating in these wards, which is useful in establishment of preventive measures against MRSA transmission.
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http://dx.doi.org/10.1016/S2221-1691(13)60055-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3631755PMC
March 2013

Draft Genome Sequences of Four Nosocomial Methicillin-Resistant Staphylococcus aureus (MRSA) Strains (PPUKM-261-2009, PPUKM-332-2009, PPUKM-377-2009, and PPUKM-775-2009) Representative of Dominant MRSA Pulsotypes Circulating in a Malaysian University Teaching Hospital.

Genome Announc 2013 Jan 31;1(1). Epub 2013 Jan 31.

Medical Molecular Biology Institute (UMBI).

Here, we report the draft genome sequences of four nosocomial methicillin-resistant Staphylococcus aureus strains (PPUKM-261-2009, PPUKM-332-2009, PPUKM-377-2009, and PPUKM-775-2009) isolated from a university teaching hospital in Malaysia. Three of the strains belong to sequence type 239 (ST239), which has been associated with sustained hospital epidemics worldwide.
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http://dx.doi.org/10.1128/genomeA.00103-12DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3569319PMC
January 2013

Emergence of chikungunya seropositivity in healthy Malaysian adults residing in outbreak-free locations: chikungunya seroprevalence results from the Malaysian Cohort.

BMC Infect Dis 2013 Feb 5;13:67. Epub 2013 Feb 5.

UKM Medical Molecular Biology Institute, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia.

Background: In 1998, Malaysia experienced its first chikungunya virus (CHIKV) outbreak in the suburban areas followed by another two in 2006 (rural areas) and 2008 (urban areas), respectively. Nevertheless, there is still a lack of documented data regarding the magnitude of CHIKV exposure in the Malaysian population. The aim of this study was to determine the extent of chikungunya virus infection in healthy Malaysian adults residing in outbreak-free locations.

Methods: A cross sectional study of chikungunya (CHIK) seroprevalence was carried out in 2009 amongst The Malaysian Cohort participants living in four states (Kuala Lumpur, Selangor, Pahang and Negeri Sembilan). A total of 945 participants were randomly identified for the study. Potential risk factors for CHIK infection were determined via questionnaires, and IgG antibodies against CHIK were detected by an enzyme-linked immunosorbent assay. Logistic regression identified risk factors associated with CHIK seropositivity, while geographical information system was used for visual and spatial analysis.

Results: From the 945 serum samples tested, 5.9% was positive for CHIK IgG. Being male, Malay, rural occupancy and Negeri Sembilan residency were identified as univariate predictors for CHIK seropositivity, while multivariate analysis identified being male and rural occupancy as risk factors.

Conclusions: This study provided evidence that CHIK is slowly emerging in Malaysia. Although the current baseline seroprevalence is low in this country, increasing number of CHIK cases reported to the Malaysia Ministry of Health imply the possibility of CHIK virus becoming endemic in Malaysia.
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http://dx.doi.org/10.1186/1471-2334-13-67DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3651385PMC
February 2013

Antibacterial performance of Ag nanoparticles and AgGO nanocomposites prepared via rapid microwave-assisted synthesis method.

Nanoscale Res Lett 2012 Sep 28;7(1):541. Epub 2012 Sep 28.

School of Applied Physics, Faculty of Science and Technology, Universiti Kebangsaan Malaysia, Bangi, Selangor, 43600, Malaysia.

Silver nanoparticles and silver-graphene oxide nanocomposites were fabricated using a rapid and green microwave irradiation synthesis method. Silver nanoparticles with narrow size distribution were formed under microwave irradiation for both samples. The silver nanoparticles were distributed randomly on the surface of graphene oxide. The Fourier transform infrared and thermogravimetry analysis results showed that the graphene oxide for the AgNP-graphene oxide (AgGO) sample was partially reduced during the in situ synthesis of silver nanoparticles. Both silver nanoparticles and AgGO nanocomposites exhibited stronger antibacterial properties against Gram-negative bacteria (Salmonella typhi and Escherichia coli) than against Gram-positive bacteria (Staphyloccocus aureus and Staphyloccocus epidermidis). The AgGO nanocomposites consisting of approximately 40 wt.% silver can achieve antibacterial performance comparable to that of neat silver nanoparticles.
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http://dx.doi.org/10.1186/1556-276X-7-541DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3492123PMC
September 2012

Coordinated phenotype switching with large-scale chromosome flip-flop inversion observed in bacteria.

Proc Natl Acad Sci U S A 2012 Jun 29;109(25):E1647-56. Epub 2012 May 29.

Department of Bacteriology, Faculty of Medicine, Juntendo University, 2-1-1 Bunkyo-Ku, Tokyo, Japan.

Genome inversions are ubiquitous in organisms ranging from prokaryotes to eukaryotes. Typical examples can be identified by comparing the genomes of two or more closely related organisms, where genome inversion footprints are clearly visible. Although the evolutionary implications of this phenomenon are huge, little is known about the function and biological meaning of this process. Here, we report our findings on a bacterium that generates a reversible, large-scale inversion of its chromosome (about half of its total genome) at high frequencies of up to once every four generations. This inversion switches on or off bacterial phenotypes, including colony morphology, antibiotic susceptibility, hemolytic activity, and expression of dozens of genes. Quantitative measurements and mathematical analyses indicate that this reversible switching is stochastic but self-organized so as to maintain two forms of stable cell populations (i.e., small colony variant, normal colony variant) as a bet-hedging strategy. Thus, this heritable and reversible genome fluctuation seems to govern the bacterial life cycle; it has a profound impact on the course and outcomes of bacterial infections.
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http://dx.doi.org/10.1073/pnas.1204307109DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3382547PMC
June 2012

Screening and detection of heterogenous vancomycin intermediate Staphylococcus aureus in Hospital Kuala Lumpur Malaysia, using the glycopeptide resistance detection Etest and population analysis profiling.

Infect Dis Rep 2012 Jan 7;4(1):e20. Epub 2012 Mar 7.

Department of Microbiology and Immunology, University Kebangsaan Malaysia Medical Centre;

In a 3-month study done in Hospital Kuala Lumpur (HKL), 7 out of 320 methicillin resistant Staphylococcus aureus isolates were confirmed as heterogeneous vancomycin intermediate S. aureus (hVISA) using the glycopeptide resistance detection e-test and population analysis, giving a prevalence rate of 2.19%. This is the first report of hVISA in Malaysia.
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http://dx.doi.org/10.4081/idr.2012.e20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3892648PMC
January 2012