Yunn-Hwen Gan

Yunn-Hwen Gan
National University of Singapore | NUS · Department of Biochemistry

35.85
 · 
PhD

About

76
Publications
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Introduction
Yunn-Hwen Gan currently works at the Department of Biochemistry, National University of Singapore. Yunn-Hwen does research in Immunology, Molecular Biology and Cell Biology and Microbiology. Their current project is 'Burkholderia pseudomallei pathogenesis and host immunity'. Another interest is multidrug resistant Klebsiella pneumoniae and hypervirulent K. pneumoniae

Publications

Publications (76)
Article
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Loss of diversity in the gut microbiome can persist for extended periods after antibiotic treatment, impacting microbiome function, antimicrobial resistance and probably host health. Despite widespread antibiotic use, our understanding of the species and metabolic functions contributing to gut microbiome recovery is limited. Using data from 4 disco...
Article
Full-text available
Burkholderia pseudomallei is the causative agent of melioidosis, an infectious disease in the tropics and subtropics with high morbidity and mortality. The facultative intracellular bacterium induces host cell fusion through its type VI secretion system 5 (T6SS5) as an important part of its pathogenesis in mammalian hosts. This allows it to spread...
Article
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The convergence of carbapenem-resistance and hypervirulence genes in Klebsiella pneumoniae has led to the emergence of highly drug-resistant superbugs capable of causing invasive disease. We analyzed 556 carbapenem-resistant K. pneumoniae isolates from patients in Singapore hospitals during 2010-2015 and discovered 18 isolates from 7 patients also...
Article
Carbapenem‐resistant Gram‐negative bacteria (GNB) are heading the list of pathogens for which antibiotics are the most critically needed. Many antibiotics are either unable to penetrate the outer‐membrane or are excluded by efflux mechanisms. Here, we report a cationic block beta‐peptide (PAS8‐ b ‐PDM12) that reverses intrinsic antibiotic resistanc...
Article
Carbapenem‐resistant Gram‐negative bacteria (GNB) are heading the list of pathogens for which antibiotics are the most critically needed. Many antibiotics are either unable to penetrate the outer‐membrane or are excluded by efflux mechanisms. Here, we report a cationic block beta‐peptide (PAS8‐ b ‐PDM12) that reverses intrinsic antibiotic resistanc...
Article
Full-text available
Hypervirulent Klebsiella pneumoniae (hvKP) causes Klebsiella‐induced liver abscess. Capsule is important for the pathogenesis of Klebsiella in systemic infection, but its role in gut colonisation is not well understood. By generating ΔwcaJ, Δwza and Δwzy capsule‐null mutants in a prototypical K1 hypervirulent isolate, we show that inactivation of w...
Article
Klebsiella pneumoniae induced liver abscess (KLA) is emerging as a leading cause of pyogenic liver abscess worldwide. In recent years, the emergence of hypervirulent K. pneumoniae (hvKp) has been strongly associated with KLA. Unlike classical K. pneumoniae which generally infects the immunocompromised population, hvKp can cause serious and invasive...
Article
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Glutathione is a low molecular weight thiol that is important for maintaining intracellular redox homeostasis. Some bacteria are able to import exogenous glutathione as a nutritional source and to counter oxidative stress. In cytosolic pathogens Burkholderia pseudomallei and Listeria monocytogenes, host glutathione regulates bacterial virulence. In...
Article
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TIP60 is a lysine acetyltransferase and is known to be a haplo-insufficient tumor suppressor. TIP60 downregulation is an early event in tumorigenesis which has been observed in several cancer types including breast and colorectal cancers. However, the mechanism by which it regulates tumor progression is not well understood. In this study, we identi...
Article
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Severe liver abscess infections caused by hypervirulent clonal-group CG23 Klebsiella pneumoniae have been increasingly reported since the mid-1980s. Strains typically possess several virulence factors including an integrative, conjugative element ICEKp encoding the siderophore yersiniabactin and genotoxin colibactin. Here we investigate CG23's evol...
Preprint
Full-text available
Dysbiosis in the gut microbiome due to antibiotic usage can persist for extended periods of time, impacting host health and increasing the risk for pathogen colonization. The specific factors associated with variability in gut microbiome recovery remain unknown. Using data from 4 different cohorts in 3 continents comprising >500 microbiome profiles...
Article
Bacteria use various endogenous antioxidants for protection against oxidative stress associated with environmental survival or host infection. Although glutathione (GSH) is the most abundant and widely used antioxidant in Proteobacteria, ergothioneine (EGT) is another microbial antioxidant, mainly produced by fungi and Actinobacteria. The Burkholde...
Article
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Cycle inhibiting factors (Cifs) are type III secretion system effectors produced by some Gram-negative pathogenic bacteria including Burkholderia pseudomallei Through their deamidase activity, Cifs inhibit the activity of Cullin RING E3 ubiquitin ligases (CRL). CRL inhibition induces the accumulation of cell cycle inhibitors p21 and p27, thereby le...
Article
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Melioidosis is a notifiable infectious disease registered with the Ministry of Health (MOH) and Agri-Food & Veterinary Authority (AVA), Singapore. From a clinical perspective, increased awareness of the disease has led to early detection and treatment initiation, thus resulting in decreasing mortality rates in recent years. However, the disease sti...
Article
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The major risk factor for Klebsiella liver abscess (KLA) is type 2 diabetes mellitus (DM), but the immunological mechanisms involved in the increased susceptibility are poorly defined. We investigated the responses of neutrophils and peripheral blood mononuclear cells (PBMCs) to hypervirulent Klebsiella pneumoniae (hvKP), the causative agent of KLA...
Article
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The anti-proliferative agent hexamethylene bisacetamide (HMBA) belongs to a class of hybrid bipolar compounds developed more than 30 y ago for their ability to induce terminal differentiation of transformed cells. Recently, HMBA has also been shown to trigger HIV transcription from latently infected cells, via a CDK9/HMBA inducible protein-1 depend...
Article
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Burkholderia pseudomallei is a serum-resistant Gram-negative bacterium capable of causing disseminated infections with metastatic complications. However, their interaction with non-phagocytic cells is poorly understood. We observed that exposure of B. pseudomallei and the closely related yet avirulent B. thailandensis to human plasma increased epit...
Article
Full-text available
Cycle inhibiting factors (Cifs) are virulence proteins secreted by the type III secretion system of some Gram-negative pathogenic bacteria including Burkholderia pseudomallei. Cif is known to function to deamidate Nedd8, leading to inhibition of Cullin E3 ubiquitin ligases (CRL) and consequently induction of cell cycle arrest. Here we show that Cif...
Article
The anti-proliferative agent hexamethylene bisacetamide (HMBA) belongs to a class of hybrid bipolar compounds developed more than 30 y ago for their ability to induce terminal differentiation of transformed cells. Recently, HMBA has also been shown to trigger HIV transcription from latently infected cells, via a CDK9/HMBA inducible protein-1 depend...
Article
The anti-proliferative agent hexamethylene bisacetamide (HMBA) belongs to a class of hybrid bipolar compounds developed more than 30 y ago for their ability to induce terminal differentiation of transformed cells. Recently, HMBA has also been shown to trigger HIV transcription from latently infected cells, via a CDK9/HMBA inducible protein-1 depend...
Article
Full-text available
Hypervirulent Klebsiella pneumoniae is an emerging cause of community-acquired pyogenic liver abscess. First described in Asia, it is now increasingly recognized in Western countries, commonly afflicting those with Asian descent. This raises the question of genetic predisposition versus geospecific strain acquisition. We leveraged on the Antibiotic...
Article
Type VI secretion systems (T6SSs) are major virulence mechanisms in many Gram-negative bacteria, but the physiological signals that activate them are not well understood. The T6SS1 of Burkholderia pseudomallei is essential for pathogenesis in mammalian hosts and is only expressed when the bacterium is intracellular. We found that signals for T6SS1...
Article
Full-text available
The Type VI Secretion System cluster 1 (T6SS1) is essential for the pathogenesis of Burkholderia pseudomallei, the causative agent of melioidosis, a disease endemic in the tropics. Inside host cells, B. pseudomallei escapes into the cytosol and through T6SS1, induces multinucleated giant cell (MNGC) formation that is thought to be important for bac...
Article
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Background Burkholderia pseudomallei is a facultative intracellular pathogen and the causative agent of melioidosis. A conserved type III secretion system (T3SS3) and type VI secretion system (T6SS1) are critical for intracellular survival and growth. The T3SS3 and T6SS1 genes are coordinately and hierarchically regulated by a TetR-type regulator,...
Article
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Type 2 diabetic patients have increased susceptibility to melioidosis, an infectious disease caused by Burkholderia pseudomallei. We had previously shown that peripheral blood mononuclear cells (PBMCs) from diabetic patients with poor glycemic control had a defective IL-12 and IFNγ response to B. pseudomallei infection, resulting in poor intracellu...
Article
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Background Burkholderia pseudomallei is the causative agent of melioidosis, a potentially fatal disease endemic in Southeast Asia and Northern Australia. This Gram-negative pathogen possesses numerous virulence factors including three “injection type” type three secretion systems (T3SSs). B. pseudomallei has been shown to activate NFκB in HEK293T c...
Article
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Globally, the number of people with Type 2 diabetes (T2D) or diabetes mellitus is projected to grow to 366–440 million by 2030, with three quarters of the increase in low- to middle-income countries [1]. The burden of communicable diseases is concentrated in low-income and resource-strapped regions, and one could predict that diabetes-related infec...
Article
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Burkholderia pseudomallei (Bp), the causative agent of the often-deadly infectious disease melioidosis, contains one of the largest prokaryotic genomes sequenced to date, at 7.2 Mb with two large circular chromosomes (1 and 2). To comprehensively delineate the Bp transcriptome, we integrated whole-genome tiling array expression data of Bp exposed t...
Article
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Burkholderia pseudomallei is a Gram-negative soil bacterium that infects both humans and animals. Although cell culture studies have revealed significant insights into factors contributing to virulence and host defense, the interactions between this pathogen and its intact host remain to be elucidated. To gain insights into the host defense respons...
Article
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The in vitro evolution and engineering of quorum-quenching lactonases with enhanced reactivities was achieved using a thermostable GKL enzyme as template, yielding the E101G/R230C GKL mutant with increased catalytic activity and broadened substrate range [Chow, J. Y., Xue, B., Lee, K. H., Tung, A., Wu, L., Robinson, R. C., and Yew, W. S. (2010) J B...
Article
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Individuals with type 2 diabetes are at increased risk of acquiring melioidosis, a disease caused by Burkholderia pseudomallei infection. Although up to half of melioidosis patients have underlying diabetes, the mechanisms involved in this increased susceptibility are unknown. We found that B. pseudomallei-infected PBMCs from diabetic patients were...
Article
Cycle inhibiting factor (Cif) is produced by pathogenic intracellular bacteria and injected into the host cells via a type III secretion system. Cif is known to interfere with the eukaryotic cell cycle by inhibiting the function of cullin RING E3 ubiquitin ligases (CRLs). Cullin proteins form the scaffold protein of CRLs and are modified with the u...
Article
Full-text available
Type III and type VI secretion systems (T3SSs and T6SSs, respectively) are critical virulence determinants in several Gram-negative pathogens. In Burkholderia pseudomallei, the T3SS-3 and T6SS-1 clusters have been implicated in bacterial virulence in mammalian hosts. We recently discovered a regulatory cascade that coordinately controls the express...
Article
Full-text available
Melioidosis is a severe infectious disease caused by the saprophytic facultative intracellular pathogen Burkholderia pseudomallei. The disease is endemic in Southeast Asia and Northern Australia, and no effective vaccine exists. To describe human cell-mediated immune responses to B. pseudomallei and to identify candidate antigens for vaccine develo...
Article
Burkholderia pseudomallei is a highly versatile pathogen capable of infecting many species of animals and plants. It is the causative agent of melioidosis, a medically important infectious disease in humans with a wide spectrum of disease manifestations. Its versatility as a pathogen is reflected in its huge 7.2Mb genome and the many virulence mech...
Article
Full-text available
Burkholderia pseudomallei is a Gram-negative saprophyte that is the causative agent of melioidosis, a severe infectious disease endemic in Northern Australia and Southeast Asia. This organism has sparked much scientific interest in the West because of its classification as a potential bioterrorism agent by the U.S. Centers for Disease Control and P...
Article
A major and critical virulence determinant of many Gram-negative bacterial pathogens is the Type III Secretion Systems (T3SS). T3SS3 in Burkholderia pseudomallei is critical for bacterial virulence in mammalian infection models but its regulation is unknown. B. pseudomallei is the causative agent of melioidosis, a potentially fatal disease endemic...
Article
Full-text available
Burkholderia pseudomallei is the causative agent for melioidosis, a disease with significant mortality and morbidity in endemic regions. Its versatility as a pathogen is reflected in its relatively huge 7.24 Mb genome and the presence of many virulence factors including three Type Three Secretion Systems known as T3SS1, T3SS2 and T3SS3. Besides bei...
Article
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The gram-negative rod Burkholderia pseudomallei is the causative agent of melioidosis, a potentially fatal disease which is endemic in tropical and subtropical areas. The bacterium multiplies intracellularly within the cytosol, induces the formation of actin tails, and can spread directly from cell to cell. Recently, it has been shown that B. pseud...
Article
Recent reports of the increase in peripheral blood γδ T cells in HIV+ patients prompted us to examine the γδ T cell system in rhesus monkeys (Macaca mulatta) and the responses of these cells to SIV infection. Our results reveal differences in the γδ T cell subset composition and their expression of CD8 in the peripheral blood of monkeys and humans....
Article
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Burkholderia pseudomallei is the causative agent of melioidosis. While adaptive immunity has been shown to be important for host resistance to B. pseudomallei, the direct interaction of the bacteria with adaptive immune cells such as T and B cells is not well known. To address this question, we infected Jurkat T cells, as well as human primary CD4+...
Article
Full-text available
Burkholderia pseudomallei is the causative agent of melioidosis, an infectious disease that can result in asymptomatic, chronic, or acute illness. In acute melioidosis, high levels of proinflammatory cytokines and chemokines are found in organs and blood, and neutrophils play a key role in controlling the infection. We showed that B. pseudomallei a...
Article
Heat shock proteins (Hsp) 60 and 70 have been intensively studied for their ability to activate innate immunity. Heat shock proteins had been shown to induce the activation of dendritic cells, T cells, and B cells. However, the possible contamination of endotoxin in heat shock protein preparations makes their function as an activator of immune syst...
Article
Full-text available
Burkholderia pseudomallei is the causative agent for melioidosis. For many bacterial infections, cytokine dysregulation is one of the contributing factors to the severe clinical outcomes in the susceptible hosts. The C57BL/6 and BALB/c mice have been established as a differential model of susceptibility in murine melioidosis. In this study, we comp...
Article
Melioidosis is an infectious disease endemic in tropical and subtropical areas but is most often described in Southeast Asia and northern Australia. It has increasingly gained attention in the Western Hemisphere because of its potential use as a biological weapon. Progress in our understanding of the virulence mechanisms of Burkholderia pseudomalle...
Article
Burkholderia pseudomallei is the causative agent for melioidosis, an infectious disease endemic in South-east Asia and northern Australia. Infection can result in a wide spectrum of clinical outcomes, including asymtomatic, acute or chronic conditions. The ability of the bacteria to survive intracellularly within phagocytes and non-phagocytes is po...
Article
Senior undergraduates in the honors or graduation year with an intention to further their career in science would soon face the real world of scientific research as a junior scientist. It is important to acquaint these students with and adequately prepare them for the key aspects of a scientist's professional life. These include technical capacitie...
Article
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Melioidosis is a life-threatening bacterial infection caused by Burkholderia pseudomallei. Some antibiotics used to treat melioidosis can induce filamentation in B. pseudomallei. Despite studies on the mechanism of virulence of the bacteria, the properties of B. pseudomallei filaments and their impact on virulence have not been investigated before....
Article
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BpsIR, a LuxIR quorum-sensing homolog, is required for optimal expression of virulence and secretion of exoproducts in Burkholderia pseudomallei. Cell density-dependent expression of bpsI and bpsR, the positive regulation of bpsIR expression by BpsR, and the synthesis of N-octanoyl-homoserine lactone (C8HSL) by BpsI are described in this report.
Article
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Heat shock proteins (HSP) have been shown to enhance antigen processing and presentation through their association with antigenic peptides and delivery of these moieties into major histocompatibility complex class I pathways. In this study, mycobacterial Hsp65 is demonstrated to have the ability to help cross-present an exogenous protein by dendrit...
Article
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Burkholderia pseudomallei, a facultatively intracellular pathogen, is a flagellated and motile gram-negative bacterium and is the causative agent of melioidosis in humans. Flagella are commonly recognized as important virulence determinants expressed by bacterial pathogens since the motility phenotype imparted by these organelles often correlates w...
Article
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Article
The environmental saphrophyte Burkholderia pseudomallei is the causative agent of melioidosis, a systemic, potentially life-threatening condition endemic to many parts of south-east Asia and northern Australia. We have used the soil nematode Caenorhabditis elegans as a model host to characterize the mechanisms by which this bacterium mounts a succe...
Article
Full-text available
Burkholderia pseudomallei is the causative agent of melioidosis, an infectious disease with protean clinical manifestations. The major route of infection is thought to be through subcutaneous inoculation of contaminated soil and water, although ingestion and inhalation of contaminated aerosols are also possible. This study examines infection throug...
Article
Full-text available
T cells undergo activation-induced cell death (AICD) through repeated stimulation of their T cell receptors (TCRs). Activated human gammadelta T cells were found to die by apoptosis when their TCRs were cross-linked by antibodies, whereas naïve gammadelta T cells freshly isolated from blood did not. Therefore, we investigated the factors that could...
Article
In recent years, heat shock proteins have been shown to be effective in enhancing the immunogenicity of tumors. In this study, we examined the effect of mycobacterial hsp65 gene transfection in a non-immunogenic and aggressive tumor cell-line in order to understand the factors that could contribute to the increase in immunogenicity mediated by Hsp6...
Article
Activated gammadelta T cells undergo apoptosis upon restimulation of their T cell receptor (TCR)/CD3 complex. We demonstrate that in these cells, the activation-induced cell death (AICD) is mediated by Fas and Fas ligand (FasL) interaction. The activated gammadelta T cells are prone to AICD initiated by exposure to mitogens, anti-TCR/CD3 antibodies...
Article
In an attempt to clone and express proteins from the Epstein-Barr virus (EBV) cDNA library to be used as antigens in an enzyme-linked immunosorbent assay (ELISA) format to test against the antibodies found in the sera of nasopharyngeal carcinoma (NPC) patients, we have isolated and characterized three clones. All three clones expressed the same pol...
Article
Intravesical Bacillus Calmette-Guerin (BCG) immunotherapy is currently the optimal choice for aggressive superficial bladder cancer, with a 70% response rate. This study investigated whether the antitumour response elicited by BCG could be improved by the addition of recombinant interferon alpha (IFN alpha) in the subcutaneous murine MB49 bladder t...