MyMedR

Emergence of Klebsiella pneumoniae producing dual carbapenemases (NDM-1 and OXA-232) and 16S rRNA methylase (armA) isolated from a Malaysian patient returning from India

Al-Marzooq F, Ngeow YF, Tay ST

Int J Antimicrob Agents, 2015 Apr;45(4):445-6.

PMID: 25631676 DOI: 10.1016/j.ijantimicag.2014.12.013

An overview of the phenotypic and genotypic characteristics of multidrug-resistant Mycobacterium tuberculosis isolates from four Asian countries

Ang CF, Ong CS, Rukmana A, Pham Thi KL, Yap SF, Ngeow YF, et al.

J Med Microbiol, 2008 Aug;57(Pt 8):1039-1040.

PMID: 18628510 DOI: 10.1099/jmm.0.47850-0

Fulltext Draft Genome Sequence of Ochroconis constricta UM 578, Isolated from Human Skin Scraping

Chan CL, Yew SM, Na SL, Tan YC, Lee KW, Yee WY, et al.

Genome Announc, 2014;2(2).

PMID: 24744321 DOI: 10.1128/genomeA.00074-14

Ochroconis constricta is a soilborne dematiaceous fungus that has never been reported to be associated with human infection. Here we report the first draft genome sequence of strain UM 578, isolated from human skin scraping. The genomic information revealed will contribute to a better understanding of this species.

Fulltext Genome analysis of Daldinia eschscholtzii strains UM 1400 and UM 1020, wood-decaying fungi isolated from human hosts

Chan CL, Yew SM, Ngeow YF, Na SL, Lee KW, Hoh CC, et al.

BMC Genomics, 2015 Nov 18;16:966.

PMID: 26581579 DOI: 10.1186/s12864-015-2200-2

BACKGROUND: Daldinia eschscholtzii is a wood-inhabiting fungus that causes wood decay under certain conditions. It has a broad host range and produces a large repertoire of potentially bioactive compounds. However, there is no extensive genome analysis on this fungal species.

RESULTS: Two fungal isolates (UM 1400 and UM 1020) from human specimens were identified as Daldinia eschscholtzii by morphological features and ITS-based phylogenetic analysis. Both genomes were similar in size with 10,822 predicted genes in UM 1400 (35.8 Mb) and 11,120 predicted genes in UM 1020 (35.5 Mb). A total of 751 gene families were shared among both UM isolates, including gene families associated with fungus-host interactions. In the CAZyme comparative analysis, both genomes were found to contain arrays of CAZyme related to plant cell wall degradation. Genes encoding secreted peptidases were found in the genomes, which encode for the peptidases involved in the degradation of structural proteins in plant cell wall. In addition, arrays of secondary metabolite backbone genes were identified in both genomes, indicating of their potential to produce bioactive secondary metabolites. Both genomes also contained an abundance of gene encoding signaling components, with three proposed MAPK cascades involved in cell wall integrity, osmoregulation, and mating/filamentation. Besides genomic evidence for degrading capability, both isolates also harbored an array of genes encoding stress response proteins that are potentially significant for adaptation to living in the hostile environments.

CONCLUSIONS: Our genomic studies provide further information for the biological understanding of the D. eschscholtzii and suggest that these wood-decaying fungi are also equipped for adaptation to adverse environments in the human host.

Fulltext Tandem mass spectrometry detection of quorum sensing activity in multidrug resistant clinical isolate Acinetobacter baumannii

Chan KG, Cheng HJ, Chen JW, Yin WF, Ngeow YF

ScientificWorldJournal, 2014;2014:891041.

PMID: 25101326 DOI: 10.1155/2014/891041

Many Proteobacteria communicate via production followed by response of quorum sensing molecules, namely, N-acyl homoserine lactones (AHLs). These molecules consist of a lactone moiety with N-acyl side chain with various chain lengths and degrees of saturation at C-3 position. AHL-dependent QS is often associated with regulation of diverse bacterial phenotypes including the expression of virulence factors. With the use of biosensor and high resolution liquid chromatography tandem mass spectrometry, the AHL production of clinical isolate A. baumannii 4KT was studied. Production of short chain AHL, namely, N-hexanoyl-homoserine lactone (C6-HSL) and N-octanoyl-homoserine lactone (C8-HSL), was detected.

Fulltext Multiphasic strain differentiation of atypical mycobacteria from elephant trunk wash

Chan KG, Loke MF, Ong BL, Wong YL, Hong KW, Tan KH, et al.

PeerJ, 2015;3:e1367.

PMID: 26587340 DOI: 10.7717/peerj.1367

Background. Two non-tuberculous mycobacterial strains, UM_3 and UM_11, were isolated from the trunk wash of captive elephants in Malaysia. As they appeared to be identical phenotypes, they were investigated further by conventional and whole genome sequence-based methods of strain differentiation. Methods. Multiphasic investigations on the isolates included species identification with hsp65 PCR-sequencing, conventional biochemical tests, rapid biochemical profiling using API strips and the Biolog Phenotype Microarray analysis, protein profiling with liquid chromatography-mass spectrometry, repetitive sequence-based PCR typing and whole genome sequencing followed by phylogenomic analyses. Results. The isolates were shown to be possibly novel slow-growing schotochromogens with highly similar biological and genotypic characteristics. Both strains have a genome size of 5.2 Mbp, G+C content of 68.8%, one rRNA operon and 52 tRNAs each. They qualified for classification into the same species with their average nucleotide identity of 99.98% and tetranucleotide correlation coefficient of 0.99999. At the subspecies level, both strains showed 98.8% band similarity in the Diversilab automated repetitive sequence-based PCR typing system, 96.2% similarity in protein profiles obtained by liquid chromatography mass spectrometry, and a genomic distance that is close to zero in the phylogenomic tree constructed with conserved orthologs. Detailed epidemiological tracking revealed that the elephants shared a common habitat eight years apart, thus, strengthening the possibility of a clonal relationship between the two strains.

Fulltext Bacterial infection of central venous catheters in short-term total parenteral nutrition

Chan L, Ngeow YF, Parasakthi N

Med J Malaysia, 1998 Mar;53(1):10-5.

PMID: 10968131

Fourteen severely ill ventilated patients in an intensive care unit, requiring short-term total parenteral nutrition, were examined for catheter-related infection. Microbiological analysis using Maki's SQ technique was carried out on catheter exit site, catheter hub, proximal subcutaneous segment of catheter and catheter up. Qualitative cultures were carried out on total parenteral nutrition and peripheral blood samples. Twenty six of 29 catheters removed (90%) were culture positive but only 7 catheters were related to positive blood cultures, giving a catheter-related bacteremia (CRB) rate of 24%. Haematogenous seeding was strongly implicated in 7/29 (24%) of catheters. Patients' skin flora appeared to be the main source of catheter-related infection. The organisms isolated for patients with CRB included coagulase-negative staphylococci, Acinetobacter and Klebsiella. It is suggested that to control infective complications of central venous catheters, emphasis should be focused on specialised intravenous therapy teams and the use of strict protocols for insertion and care of central lines.

Fulltext Evaluation of the bacteriological contamination of a closed feeding system for enteral nutrition

Chan L, Yasmin AH, Ngeow YF, Ong GS

Med J Malaysia, 1994 Mar;49(1):62-7.

PMID: 8057993

A closed enteral delivery system consisting of a cardboard tetrapack containing the sterile ready-to-use liquid feed and an independent sterile administration set, has been devised. We found bacterial contamination within 24 hours in this system in patients on ventilatory support in intensive care. This emphasises the need for meticulous care in handling enteral feeding systems to prevent environmental contamination.

Mycoplasma Pneumoniae infection in Malaysian children admitted with community acquired pneumonia

Chan PW, Lum LC, Ngeow YF, Yasim MY

Southeast Asian J. Trop. Med. Public Health, 2001 Jun;32(2):397-401.

PMID: 11556595

Mycoplasma pneumoniae is increasingly recognized as an important cause of community acquired pneumonia (CAP) in children. We determined the importance of M. pneumoniae as a causative agent in 170 children aged 1 month to 15 years who were hospitalized with CAP over a 6-month period. The diagnosis of M. pneumoniae infection was based on serological evidence obtained by a particle agglutination test (SERODIA-MYCO II). A positive serological diagnosis was made if the acute phase serum titer was more than 1:160 or paired samples taken 2-4 weeks apart showed a four-fold or greater rise in the serum titer. M. pneumoniae was identified as the causative agent in 40 (23.5%) children. Children with M. pneumoniae infection were more likely to be older than 3 years (OR 4.0 95%CI 1.8-9.1, p<0.001), Chinese (OR 4.3 95%CI 2.0-8.9, p<0.001), have a duration of illness longer than 7 days prior to admission (OR 6.0 95%CI 2.7-13.5, p<0.001) and have perihilar interstitial changes on chest X-ray (OR 4.6 95%CI 2.2-9.9, p<0.001). A significant number of hospital admissions for CAP in Malaysian children can be attributed to M. pneumoniae. It is important to identify these children so as to administer the most appropriate antibiotic treatment.

Heat inactivation of serum potentiates anti-cardiolipin antibody binding in ELISA

Cheng HM, Ngeow YF, Sam CK

J Immunol Methods, 1989 Nov 30;124(2):235-8.

PMID: 2600427

Heat treatment of sera at 56 degrees C for 30 min results in positive ELISA reactions for anti-cardiolipin antibody (aCL) in sera that had undetectable or low levels of aCL before heat inactivation. The positive, potentiated reactivity of the heated sera in the aCL ELISA could be inhibited with the cardiolipin antigen and was abolished by prior IgG depletion using staphylococcal protein A. The heat-potentiating effect of aCL binding in ELISA was evident in both normal human sera and clinical sera including sera from patients with systemic lupus erythematosus and syphilis.

IgA antiphospholipid antibodies in normal human saliva cross-react with bacterial lipopolysaccharide

Cheng HM, Ngeow YF

Int Arch Allergy Immunol, 1993;101(3):297-8.

PMID: 8324391

Fulltext Atypical pneumonia due to Chlamydia pneumoniae: a case report

Cheong YM, Wong WK, Ngeow YF

Singapore Med J, 1993 Aug;34(4):352-3.

PMID: 8266214

A first case of Chlamydia pneumoniae pneumonia in Malaysia is reported. The diagnosis was made by a significant change in C. pneumoniae antibody titre. The infection responded well to a course of erythromycin.

Fulltext Genomic reconnaissance of clinical isolates of emerging human pathogen Mycobacterium abscessus reveals high evolutionary potential

Choo SW, Wee WY, Ngeow YF, Mitchell W, Tan JL, Wong GJ, et al.

Sci Rep, 2014;4:4061.

PMID: 24515248 DOI: 10.1038/srep04061

Mycobacterium abscessus (Ma) is an emerging human pathogen that causes both soft tissue infections and systemic disease. We present the first comparative whole-genome study of Ma strains isolated from patients of wide geographical origin. We found a high proportion of accessory strain-specific genes indicating an open, non-conservative pan-genome structure, and clear evidence of rapid phage-mediated evolution. Although we found fewer virulence factors in Ma compared to M. tuberculosis, our data indicated that Ma evolves rapidly and therefore should be monitored closely for the acquisition of more pathogenic traits. This comparative study provides a better understanding of Ma and forms the basis for future functional work on this important pathogen.

Fulltext Whole-Genome Shotgun Sequencing of Mycobacterium abscessus M156, an Emerging Clinical Pathogen in Malaysia

Choo SW, Wong YL, Beh CY, Lokanathan N, Leong ML, Ong CS, et al.

Genome Announc, 2013 Jan;1(1).

PMID: 23405341 DOI: 10.1128/genomeA.00063-12

Mycobacterium abscessus is an emerging clinical pathogen commonly associated with non-tuberculous mycobacterial infections. We report herein the draft genome of M. abscessus strain M156.

Fulltext Genome sequence of the Mycobacterium abscessus strain M93

Choo SW, Wong YL, Yusoff AM, Leong ML, Wong GJ, Ong CS, et al.

J Bacteriol, 2012 Jun;194(12):3278.

PMID: 22628507 DOI: 10.1128/JB.00492-12

Mycobacterium abscessus is a rapid-growing species of nontuberculous mycobacteria that is frequently associated with opportunistic infections in humans. We report herein the draft genome sequence of M. abscessus strain M93.

Analysis of the genome of Mycobacterium abscessus strain M94 reveals an uncommon cluster of tRNAs

Choo SW, Wong YL, Leong ML, Heydari H, Ong CS, Ng KP, et al.

J Bacteriol, 2012 Oct;194(20):5724.

PMID: 23012295

Mycobacterium abscessus is a species of rapidly growing nontuberculous mycobacteria that is frequently associated with opportunistic infections in humans. Here, we report the annotated genome sequence of M. abscessus strain M94, which showed an unusual cluster of tRNAs.

Fulltext Genome analysis of Mycobacterium massiliense strain M172, which contains a putative mycobacteriophage

Choo SW, Yusoff AM, Wong YL, Wee WY, Ong CS, Ng KP, et al.

J Bacteriol, 2012 Sep;194(18):5128.

PMID: 22933758 DOI: 10.1128/JB.01096-12

The genome of Mycobacterium massiliense M172, isolated from a human sputum sample, was sequenced using Illumina GA IIX technology and found to contain 5,204,460 bp, including putative genes for virulence and antibiotic resistance as well as a 92-kb genomic region most likely to correspond to a mycobacteriophage.

Fulltext Annotated genome sequence of Mycobacterium massiliense strain M154, belonging to the recently created taxon Mycobacterium abscessus subsp. bolletii comb. nov

Choo SW, Wong YL, Tan JL, Ong CS, Wong GJ, Ng KP, et al.

J Bacteriol, 2012 Sep;194(17):4778.

PMID: 22887675 DOI: 10.1128/JB.01043-12

Mycobacterium massiliense has recently been proposed as a member of Mycobacterium abscessus subsp. bolletii comb. nov. Strain M154, a clinical isolate from the bronchoalveolar lavage fluid of a Malaysian patient presenting with lower respiratory tract infection, was subjected to shotgun DNA sequencing with the Illumina sequencing technology to obtain whole-genome sequence data for comparison with other genetically related strains within the M. abscessus species complex.

Combined use of wild-type HBV precore and high serum iron marker as a potential tool for the prediction of cirrhosis in chronic hepatitis B infection

Chook JB, Ngeow YF, Yap SF, Tan TC, Mohamed R

J Med Virol, 2011 Apr;83(4):594-601.

PMID: 21328372 DOI: 10.1002/jmv.22016

Hepatitis B virus (HBV) and high liver iron deposits have both been associated with the development of cirrhosis. Among HBV factors, genotype and mutations in the basal core promoter (BCP) and precore regions have been most frequently studied but the evidence for a positive association with cirrhosis has been inconsistent. In this study, sera from persons with chronic HBV infection with and without cirrhosis were used for whole HBV genome analysis and for the estimation of serum iron marker (serum iron or ferritin) levels. Single codon analysis showed that the precore wild-type, TGG (nt 1,895-1,897), gave the highest accuracy (77.5%) for the identification of cirrhosis compared to other codons. When TGG was analyzed together with the precore start codon wild-type, ATG (nt 1,814-1,816), the accuracy was improved to 80.0% (odds ratio=35.29; 95% confidence interval=3.87-321.93; Phi=0.629; P<0.001). When the serum iron marker was included for analysis, it was clear that a combination of a precore wild-type and high serum iron marker gave a better accuracy (90.0%) (odds ratio=107.67; 95% confidence interval=10.21-1,135.59; Phi=0.804; P<0.001) for the identification of cirrhosis than either biomarker alone. It appeared that a combined use of both these biomarkers might help to predict the development of cirrhosis in a person with chronic HBV infection, but longitudinal studies are required to test this hypothesis.

Comparative analysis of viral genomes from acute and chronic hepatitis B reveals novel variants associated with a lower rate of chronicity

Chook JB, Ngeow YF, Khang TF, Ng KP, Tiang YP, Mohamed R

J Med Virol, 2013 Mar;85(3):419-24.

PMID: 23297244 DOI: 10.1002/jmv.23500

Infection with the hepatitis B virus (HBV) may lead to an acute or chronic infection. It is generally accepted that the clinical outcome of infection depends on the balance between host immunity and viral survival strategies. In order to persist, the virus needs to have a high rate of replication and some immune-escape capabilities. Hence, HBVs lacking these properties are likely to be eliminated more rapidly by the host, leading to a lower rate of chronicity. To test this hypothesis, 177 HBV genomes from acute non-fulminant cases and 1,149 from chronic cases were retrieved from GenBank for comparative analysis. Selection of candidate nucleotides associated with the disease state was done using random guess cut-off and the Bonferroni correction. Five significant nucleotides were detected using this filtering step. Their predictive values were assessed using the support vector machine classification with five-fold cross-validation. The average prediction accuracy was 61% ± 1%, with a sensitivity of 24% ± 1%, specificity of 98% ± 1%, positive predictive value of 92% ± 4% and negative predictive value of 56% ± 1%. BCP/X, enhancer I and surface/polymerase variants were found to be associated almost exclusively with acute hepatitis. These HBV variants are novel potential markers for non-progression to chronic hepatitis.

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