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Fulltext Triclosan Demonstrates Synergic Effect with Amphotericin B and Fluconazole and Induces Apoptosis-Like Cell Death in Cryptococcus neoformans

Movahed E, Tan GM, Munusamy K, Yeow TC, Tay ST, Wong WF, et al.

Front Microbiol, 2016;7:360.
PMID: 27047474 DOI: 10.3389/fmicb.2016.00360

Cryptococcus neoformans is an opportunistic fungus that causes fatal meningoencephalitis especially in AIDS patients. There is an increasing need for discovery of new anti-cryptococcal drugs due to emergence of resistance cases in recent years. In this study, we aim to elucidate the antifungal effect of triclosan against C. neoformans.
Temporal proteomic profiling of Chlamydia trachomatis-infected HeLa-229 human cervical epithelial cells

Tan GM, Lim HJ, Yeow TC, Movahed E, Looi CY, Gupta R, et al.

Proteomics, 2016 05;16(9):1347-60.
PMID: 27134121 DOI: 10.1002/pmic.201500219

Chlamydia trachomatis is the leading causative agent of bacterial sexually transmitted infections worldwide which can lead to female pelvic inflammatory disease and infertility. A greater understanding of host response during chlamydial infection is essential to design intervention technique to reduce the increasing incidence rate of genital chlamydial infection. In this study, we investigated proteome changes in epithelial cells during C. trachomatis infection by using an isobaric tags for relative and absolute quantitation (iTRAQ) labeling technique coupled with a liquid chromatography-tandem mass spectrometry (LC-MS(3) ) analysis. C. trachomatis (serovar D, MOI 1)-infected HeLa-229 human cervical carcinoma epithelial cells (at 2, 4 and 8 h) showed profound modifications of proteome profile which involved 606 host proteins. MGST1, SUGP2 and ATXN10 were among the top in the list of the differentially upregulated protein. Through pathway analysis, we suggested the involvement of eukaryotic initiation factor 2 (eIF2) and mammalian target of rapamycin (mTOR) in host cells upon C. trachomatis infection. Network analysis underscored the participation of DNA repair mechanism during C. trachomatis infection. In summary, intense modifications of proteome profile in C. trachomatis-infected HeLa-229 cells indicate complex host-pathogen interactions at early phase of chlamydial infection.
The artificial loss of Runx1 reduces the expression of quiescence-associated transcription factors in CD4(+) T lymphocytes

Wong WF, Kohu K, Nagashima T, Funayama R, Matsumoto M, Movahed E, et al.

Mol Immunol, 2015 Dec;68(2 Pt A):223-33.
PMID: 26350416 DOI: 10.1016/j.molimm.2015.08.012

The Runx1 transcription factor cooperates with or antagonizes other transcription factors and plays essential roles in the differentiation and function of T lymphocytes. Previous works showed that Runx1 is expressed in peripheral CD4(+) T cells which level declines after T cell receptor (TCR) activation, and artificial deletion of Runx1 causes autoimmune lung disease in mice. The present study addresses the mechanisms by which Runx1 contributes to the maintenance of peripheral CD4(+) T cell quiescence. Microarray and quantitative RT-PCR analyses were employed to compare the transcriptome of Runx1 -/- CD4(+) T cells to those of unstimulated and TCR-stimulated Runx1 +/- cells. The results identified genes whose expression was modulated similarly by Runx1 deletion and TCR activation. Among them, genes encoding cytokines, chemokines, and Jak/STAT signaling molecules were substantially induced. In Runx1-deleted T cells, simultaneous increases in Il-17A and Rorγc, a known master gene in TH17 differentiation, were observed. In addition, we observed that the loss of Runx1 reduced the transcription of genes encoding quiescence-associated transcription factors, including Foxp1, Foxo1, and Klf2. Interestingly, we identified consensus Runx1 binding sites at the promoter regions of Foxp1, Foxo1, and Klf2 genes, which can be enriched by chromatin immunoprecipitation assay with an anti-Runx1 antibody. Therefore, we suggest that Runx1 may activate, directly or indirectly, the expression of quiescence-associated molecules and thereby contribute to the maintenance of quiescence in CD4(+) T cells.
Fulltext Prevalence of plasmid-bearing and plasmid-free Chlamydia trachomatis infection among women who visited obstetrics and gynecology clinics in Malaysia

Yeow TC, Wong WF, Sabet NS, Sulaiman S, Shahhosseini F, Tan GM, et al.

BMC Microbiol, 2016 Mar 18;16:45.
PMID: 26987367 DOI: 10.1186/s12866-016-0671-1

BACKGROUND: The 7.5 kb cryptic plasmid of Chlamydia trachomatis has been shown to be a virulence factor in animal models, but its significance in humans still remains unknown. The aim of this study was to investigate the prevalence and potential involvement of the C. trachomatis cryptic plasmid in causing various clinical manifestations; including infertility, reproductive tract disintegrity, menstrual disorder, and polycystic ovarian syndrome (PCOS) among genital C. trachomatis-infected patients.
RESULTS:A tot l of 180 female patients of child bearing age (mean 30.9 years old, IQR:27-35) with gynecological complications and subfertility issues, who visited Obstetrics and Gynecology clinics in Kuala Lumpur, Malaysia were recruited for the study. Prevalence of genital chlamydial infection among these patients was alarmingly high at 51.1% (92/180). Of the 92 chlamydia-infected patients, 93.5% (86/92) were infected with plasmid-bearing (+) C. trachomatis while the remaining 6.5% (6/92) were caused by the plasmid-free (-) variant. Our data showed that genital C. trachomatis infection was associated with infertility issues, inflammation in the reproductive tract (mucopurulent cervicitis or endometriosis), irregular menstrual cycles and polycystic ovarian syndrome (PCOS). However, no statistical significance was detected among patients with plasmid (+) versus plasmid (-) C. trachomatis infection. Interestingly, plasmid (+) C. trachomatis was detected in all patients with PCOS, and the plasmid copy numbers were significantly higher among PCOS patients, relative to non-PCOS patients.
CONCLUSION: Our findings show a high incidence of C. trachomatis infection among women with infertility or gynecological problems in Malaysia. However, due to the low number of plasmid (-) C. trachomatis cases, a significant role of the plasmid in causing virulence in human requires further investigation of a larger cohort.
KEYWORDS: Chlamydia trachomatis; Infertility; Plasmid; Reproductive system disorders
Study site: Obstetrics and Gynecology clinic, University Malaya Medical Centre (UMMC), Kuala Lumpur, Malaysia
Erratum: prevalence of plasmid-bearing and plasmid-free chlamydia trachomatis infection among women who visited obstetrics and gynecology clinics in Malaysia

Yeow TC, Wong WF, Sabet NS, Sulaiman S, Shahhosseini F, Tan GM, et al.

BMC Microbiol, 2016 May 23;16(1):95.
PMID: 27215275
CPAF, HSP60 and MOMP antigens elicit pro-inflammatory cytokines production in the peripheral blood mononuclear cells from genital Chlamydia trachomatis-infected patients

Cheong HC, Lee CYQ, Cheok YY, Shankar EM, Sabet NS, Tan GMY, et al.

Immunobiology, 2019 01;224(1):34-41.
PMID: 30477893 DOI: 10.1016/j.imbio.2018.10.010

BACKGROUND: Persistent inflammation caused by Chlamydia trachomatis in the female genital compartment represents one of the major causes of pelvic inflammatory disease (PID), ectopic pregnancy and infertility in females. Here, we examined the pro-inflammatory cytokine response following stimulation with three different types of C. trachomatis antigens, viz. chlamydial protease-like factor (CPAF), heat shock protein 60 (HSP60) and major outer membrane protein (MOMP).
METHODS: A total of 19 patients with genital C. trachomatis infection and 10 age-matched healthy controls were recruited for the study. Peripheral blood mononuclear cells (PBMCs) isolated from genital C. trachomatis-infected females were cultured in the presence of CPAF, HSP60 and MOMP antigens, and cytokines were measured by ELISA assay.
RESULTS: We reported that pro-inflammatory cytokines (TNF-α, IL-1β and IL-6) were robustly secreted following antigenic exposure. Notably, CPAP and MOMP were more potent in triggering IL-1β, as compared to HSP60. Elevated levels of the proinflammatory cytokines were also noted in the samples infected with plasmid-bearing C. trachomatis as compared to those infected with plasmid-free strains.
CONCLUSIONS: Our study highlights distinct ability of chlamydial antigens in triggering pro-inflammatory response in the host immune cells.