Tzu-Wen Huang

Taipei Medical University | TMU · Department of Microbiology and Immunology

Motivation Microbiota analyses have important implications for health and science. These analyses make use of 16S/18S rRNA gene sequencing to identify taxa and predict species diversity. However, most available tools for analyzing microbiota data require adept programming skills and in-depth statistical knowledge for proper implementation. While lo...

The overuse of antibiotics has resulted in the emergence of antibiotic resistance, not only in bacteria but also in fungi. Streptomyces are known to produce numerous secondary metabolites including clinically useful antibiotics. In this study, we screened for antibiotic-producing actinobacteria from soils in Taipei and discovered a Streptomyces str...

Chitosan (CS) electrospun nanofiber (ENF) membranes were modified with fucoidan (Fu) and CuS NPs through polyelectrolyte complexation and genipin (GP)-involved cross-linking reaction. The formation of Fu/CS complex and cross-linking of CS with GP increased the acid resistance and reduced the swelling rate of CS ENF, while the covalent conjugation o...

This study analyzed the genetic diversity of ciprofloxacin (CIP) nonsusceptibility and the relationship between two major mechanisms and minimum inhibitory concentrations (MICs) of CIP in nontyphoidal Salmonella (NTS). Chromosomal mutations in quinolone resistance-determining regions (QRDRs) and plasmid-mediated quinolone resistance (PMQR) genes we...

Background Macrophages play crucial roles in immune responses during the course of schistosomal infections. Methods We currently investigated influence of immunocompetent changes in macrophages via microarray-based analysis, mRNA expression analysis, detection of serum cytokines, and subsequent evaluation of the immune phenotypes following the dif...

Acinetobacter baumannii, a Gram-negative bacterium, is an important nosocomial pathogen. Colistin-resistant A. baumannii is becoming a new concern, since colistin is one of the last-line antibiotics for infections by carbapenem-resistant A. baumannii. From 452 carbapenem-resistant isolates collected in a teaching hospital in Taipei, Taiwan, we iden...

Spurred by recent progress in biomaterials and therapeutics, stimulus-responsive strategies that deliver an active substance in temporal-, spatial-, and dose-controlled fashions have become achievable. Implementation of such strategies necessitates the use of bio-safe materials that are sensitive to a specific pathological incitement or that, in re...

Background: Heterogeneous features of lung adenocarcinoma (LUAD) are used to stratify patients into terminal respiratory unit (TRU), proximal-proliferative (PP), and proximal-inflammatory (PI) subtypes. A more-accurate subtype classification would be helpful for future personalized medicine. However, these stratifications are based on genes with va...

Background Carbapenem-resistant Acinetobacter species have emerged as notorious pathogens causing nosocomial infections. Several phenotypic methods have been developed for detecting carbapenemase production in Enterobacteriaceae. The accuracy of these methods in the prediction of carbapenemase production in Acinetobacter species has not been studie...

The need for new antibiotics is increasing due to their overuse, and antibiotic resistance has become one of the major threats worldwide to public health, food safety, and clinical treatment. In this study, we describe an actinobacterial isolate, YX44, which belongs to the genus Streptomyces. This Streptomyces was isolated from a drinking pipe loca...

Aims Immune checkpoints regulate immunity to prevent autoimmunity and protect the host from damage during pathogenic infection. They also participate in subverting immune surveillance and promote antitumor immunity in cancers. Although immunotherapy improves clinical outcomes, not all cancer patients experience expected responses after therapy. Hen...

Background Long noncoding (lnc)RNAs and glycolysis are both recognized as key regulators of cancers. Some lncRNAs are also reportedly involved in regulating glycolysis metabolism. However, glycolysis-associated lncRNA signatures and their clinical relevance in cancers remain unclear. We investigated the roles of glycolysis-associated lncRNAs in can...

Objectives Acinetobacter seifertii, a new member of the Acinetobacter baumannii group, has emerged as a cause of severe infections in humans. We investigated the clinical and molecular characteristics of A. seifertii. Patients and methods This retrospective study enrolled 80 adults with A. seifertii bloodstream infection (BSI) at four medical cent...

Objectives: Emergent antimicrobial-resistant hypervirulent Klebsiella pneumoniae (hvKp) is an important public health issue. We aimed to investigate resistance mechanisms and hypervirulent traits among tigecycline-non-susceptible (TNS) K. pneumoniae clinical strains, focusing on one hvKp strain with in vivo evolution of tigecycline resistance. Me...

Purpose To investigate the role of sonic hedgehog (Shh) signaling and epithelial–mesenchymal transition (EMT) in bladder cancer progression and invasion. Methods We cultured three bladder cancer cell lines, muscle-invasive T24 and 5637, and non-muscle-invasive KK47, in the presence of a recombinant-Shh (r-Shh) protein or cyclopamine, a Shh signali...

Tumor-infiltrating lymphocytes are related to positive clinical prognoses in numerous cancer types. Programmed death ligand 1 (PD-L1), a mediator of the PD-1 receptor, plays an inhibitory role in cancer immune responses. PD-L1 upregulation can impede infiltrating T-cell functions in lung adenocarcinoma (LUAD), a lung cancer subtype. However, associ...

The effect of biofilm formation on bacteraemic pneumonia caused by A. baumannii is unknown. We conducted a 4-year multi-center retrospective study to analyze 71 and 202 patients with A. baumannii bacteraemic pneumonia caused by biofilm-forming and non-biofilm-forming isolates, respectively. The clinical features and outcomes of patients were invest...

Carbapenem-resistant Acinetobacter baumannii (CRAB) has increased significantly in recent decade in Taiwan. This study investigated the molecular epidemiology of CRAB with focus on the mechanisms of resistance and spread in isolates with blaOXA-23-like or blaOXA-24-like . All 555 CRAB isolates in our 2002-2010 multi-centered collection were tested...

Absatract Along with the constant improvement in high-throughput sequencing technology, an increasing number of transcriptome sequencing projects are carried out in organisms without decoded genome information and even on environmental biological samples. To study the biological functions of novel transcripts, the very first task is to identify the...

To investigate the link between two NDM-1-positive Acinetobacter isolates from the same hospital, the plasmid profiles of the isolates were examined. These two isolates were found from a surveillance programme within 3 months from two patients without obvious physical contact or hospitalization time overlap. Antimicrobial susceptibility tests, geno...

Klebsiella pneumoniae is a leading cause of hospital-acquired urinary tract infections and pneumonia worldwide, and is responsible for many cases of pyogenic liver abscess among diabetic patients in Asia. A defining characteristic of this pathogen is the presence of a thick, exterior capsule that has been reported to play a role in biofilm formatio...

Filamentous bacteria of the genus Streptomyces possess linear chromosomes and linear plasmids. Theoretically, linear replicons may not need a decatenase for post-replicational separation of daughter molecules. Yet, Streptomyces contain parC and parE that encode the subunits for the decatenase topoisomerase IV. The linear replicons of Streptomyces a...

Genetic determinants of a blaNDM-1-positive, multidrug-resistant bacterial isolate that caused active infection was investigated by DNA sequencing. Two plasmids, pKOX_NDM1 and pKOX-R1, were identified for the Klebsiella oxytoca strain E718. Sequence annotation revealed a blaNDM-1 gene in pKOX_NDM1 and two extended-spectrum β-lactamase producers (bl...

The genetic features of the antimicrobial resistance of a multidrug resistant Klebsiella pneumoniae strain harboring bla NDM-1 were investigated to increase our understanding of the evolution of NDM-1. The strain, KPX, came from a Taiwanese patient with a hospitalization history in New Delhi. Complete DNA sequencing was performed; and the genes res...

Identification of the genetic determinants for amikacin resistance. The predicted amikacin resistance genes are colored orange. These include a gene encoding a putative rRNA methyltransferase, rmt, and aac(6′)-Ib on pKPX-1, and a aac(6′)-Ib-cr gene on pKPX-2. Both ends of the insert in each resistant clone were sequenced, and the sequence pairs map...

Identification of genetic determinants for chloramphenicol resistance. The predicted chloramphenicol resistance genes are colored green. Both ends of the insert in each resistant clone were sequenced, and the sequence pairs mapped back to the complete plasmid sequences. The genomic regions covered by the resistant clones are indicated by dotted lin...

The breakpoint at the NDM-1 region. The remaining sequence of the amplified DNA fragment after losing the NDM-1 region is shown. The arrows indicate the orientation of the repeat-flanking coding sequences (109 and 114). Gray color indicates the 1543-bp repeat identified in the NDM-1 region (as shown in Fig. 3A). (TIF)

Background The increasing number of infections caused by strains of Klebsiella pneumoniae that are resistant to multiple antibiotics has developed into a major medical problem worldwide. The development of next-generation sequencing technologies now permits rapid sequencing of many K. pneumoniae isolates, but sequence information alone does not pro...

List of all RNAP binding sites and their associated RTSs.

List of all RpoS binding sites and their associated RTSs.

List of putative ORFs.

List of antisense transcripts.

Expression level differences between exponential versus stationary phase for the five sigma factors and known virulence genes.

List of all RTSs detected during this study.

RTSs containing more than one TSS.

List of putative sRNAs.

RTS and chIP-chip data for known virulence genes.

List of all RpoD binding sites and their associated RTSs.

The phosphate starvation response in bacteria has been studied extensively for the past few decades and the phosphate-limiting signal is known to be mediated via the PhoBR two-component system. However, the global DNA binding profile of the response regulator PhoB and the PhoB downstream responses are currently unclear. In this study, chromatin imm...

Purity data for purification of PhoB-His fusion protein. This figure displays the (A) SDS-PAGE and (B) the western blot results to demonstrate the purity of our purified PhoB-His fusion protein. The lanes from left to right are Marker (M), cell lysate (CL), flow-through (FT), the first washed fraction (W1), the second washed fraction (W2), the firs...

List of plasmids used in this study. (DOC)

List of oligonucleotides used in this study. (DOC)

The genome-wide profile of PhoB binding regions across the E. coli genome. (A) An overview of the results from ChIP-chip experiments at an OD600 value of 1.0. The log2 fold change (y-axis) is the log2 ratio (grey line) of the normalized Cy5 signal (MG1655_PhoB_FLAG) divided by the normalized Cy3 signal (MG1655) after averaging our triplicate result...

A non-preferred binding region of PhoB. In addition to PhoB binding regions, there is a long region in which the PhoB binding signals are lower than background noises. This region ranges from the genomic location of 1292000 to 1306000 bps. The y-axis represents the log2 ratio (grey line) and the smoothed ratio (black line) of the normalized Cy5 sig...

Novel PhoB bindings located in the coding regions may participate in gene regulation. The three genes, yahA (i), cof (ii), and yddV (iii), were shown to be differentially expressed in our gene expression microarray analysis. From our ChIP-chip analysis, significant PhoB binding peaks were detected and the putative PhoB binding motifs were also iden...

PhoB-FLAG fusion protein in MG1655_PhoB_FLAG strain has the same activity as PhoB in MG1655 wild type strain. In order to confirm that the activity of our PhoB-FLAG fusion protein is not affected by the C-terminal FLAG tag, a reporter gene assay was used to measure the activity of the self-regulated PhoB promoter. The constructed phoB promoter::luc...

List of differentially expressed genes identified from the microarray analysis. (DOCX)

We report the complete genome sequence of Klebsiella oxytoca E718, a New Delhi metallo-β-lactamase-1 (NDM-1)-producing strain isolated from a renal transplant patient. The genome contains a 6,097,032-bp chromosome and two multidrug resistance plasmids with sizes of 324,906 bp and 110,781 bp.

We report the complete genome sequence of M013, a representative strain of a pvl-positive, sequence type 59-staphylococcal cassette chromosome mec type V (ST59-SCCmec type V) community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) clone in Taiwan. Comparison of M013 with the genomes of two CA-MRSA strains in the United States rev...

Klebsiella pneumoniae is a Gram-negative bacterium of the family Enterobacteriaceae that possesses diverse metabolic capabilities: many strains are leading causes of hospital-acquired infections that are often refractory to multiple antibiotics, yet other strains are metabolically engineered and used for production of commercially valuable chemical...

Bidirectional replication of the linear chromosomes and plasmids of Streptomyces spp. results in single-strand overhangs at their 3′ ends, which contain extensive complex palindromic sequences. The overhangs are believed to be patched by DNA synthesis primed by a terminal protein that remains covalently bound to the 5′ ends of the telomeres. We dis...

Both polA (encoding DNA polymerase I; Pol I) and a paralog were deleted from Streptomyces strains. Despite the UV sensitivity and slow growth caused by the ΔpolA mutation, the double mutant was viable. Thus, in contrast to a previous postulate, Pol I and its paralog are not essential for replication of Streptomyces chromosomes.

Single-stranded gaps at the 3′ ends of Streptomyces linear replicons are patched by DNA synthesis primed by terminal proteins (TP) during replication. We devised an in vitro system that specifically incorporated dCMP, the first nucleotide at the 5′ ends, onto a threonine residue of the TP of Streptomyces coelicolor.

The recombinase RecA plays a crucial role in homologous recombination and the SOS response in bacteria. Although recA mutants usually are defective in homologous recombination and grow poorly, they nevertheless can be isolated in almost all bacteria. Previously, considerable difficulties were experienced by several laboratories in generating recA n...

The life cycle of Streptomyces involves the formation of filamentous substrate and aerial hyphae. Following cessation of growth of an aerial hypha, multiple septation occurs at the tip to produce a chain of unigenomic spores. A gene, shyA, which influences several aspects of this growth, was isolated and partially characterized in Streptomyces coel...