Yun-liang Yang - Academia.edu (original) (raw)

Papers by Yun-liang Yang

To understand the Candida colonization of human immunodeficiency virus (HIV)-infected outpatients... more To understand the Candida colonization of human immunodeficiency virus (HIV)-infected outpatients in Taiwan, we have conducted a prospective cohort study of Candida colonization and its risk factors at the National Taiwan University Hospital from 1999 to 2002. More than 50% of the patients were colonized with Candida species, and 12% developed symptomatic candidiasis. Patients colonized with fluconazole-resistant strains of Candida

Medical mycology, 2006

A total of 3,926 yeast isolates were isolated from 24 hospitals participating in the Taiwan Surve... more A total of 3,926 yeast isolates were isolated from 24 hospitals participating in the Taiwan Surveillance of Antimicrobial Resistance of Yeasts (TSARY) from July to September 2002. Candida albicans (69.1%) was the most common species, followed by Candida tropicalis (12.9%), Candida glabrata (8.3%), Candida parapsilosis (2.7%), Candida krusei (0.6%), and others (6.4%). To study the distribution and antifungal susceptibility of Candida species according to sources and patient ages, we have collected and analyzed the clinical data of 861 isolates. Of those 861 isolates, urine was the most common source (40%) followed by sputum (22.1%), blood (13.5%), central venous catheter (5.5%), wound (5.2%), and others (13.7%). With increasing age, we observed a significant increase in the percentage of isolates from urine (P=0.00005) and a parallel reduction from blood (P=0.009). As expected, more elder patients were hospitalized than younger ones (P=0.05). In total, 2.7% and 1.9% of isolates were ...

Diagnostic microbiology and infectious disease, 2005

Susceptibilities to amphotericin B and fluconazole of 909 Candida species collected during the Ta... more Susceptibilities to amphotericin B and fluconazole of 909 Candida species collected during the Taiwan Surveillance of Antimicrobial Resistance of Yeasts (TSARY) in 2002 were determined by the broth microdilution method. There were 395 (43.5%) Candida albicans, 244 (26.8%) C. tropicalis, 187 (20.6%) C. glabrata, 63 (6.9%) C. parapsilosis, 9 (1%) C. krusei, and 11 (1.2%) others. Among them, 23 (2.5%) isolates were resistant to amphotericin B. They consisted of 10 C. glabrata, 6 C. krusei, 3 C. albicans, 1 C. tropicalis, 1 C. parapsilosis, and 2 others. The resistance rate to amphotericin B has increased compared with that of TSARY 1999 (2.5% versus 0.5%). There were 7 C. krusei, 5 C. albicans, 3 C. glabrata, and 2 others isolates resistant to fluconazole. The resistance rate to fluconazole has decreased from 8.4% in 1999 to 1.9% in 2002. A pattern of coresistance to both amphotericin B and fluconazole was observed.

International journal of antimicrobial agents, 2004

The activity of voriconazole was determined against 285 Candida species consisting of 53 resistan... more The activity of voriconazole was determined against 285 Candida species consisting of 53 resistant isolates, 43 susceptible-dose dependent and 189 isolates susceptible to fluconazole. The MIC(50) and MIC(90) to fluconazole were 8 and 64 mg/l, respectively. The range of minimum inhibitory concentrations (MICs) to voriconazole was from 0.0325 to 2 mg/l and the MIC(50) and MIC(90) were 0.125 and 0.5 mg/l, respectively. Only 3 of 285 tested isolates had MICs to voriconazole equal to 2 mg/l. A total of 38 isolates, consisted of 3 Candida albicans, 5 Candida krusei, 7 Candida tropicalis and 21 Candida glabrata, had >/= 0.5 mg/l to voriconazole. There was correlation between the susceptibility to fluconazole and voriconazole.

Infection control and hospital epidemiology, 2004

To determine the susceptibilities of Candida species isolated from Taiwan to amphotericin B and f... more To determine the susceptibilities of Candida species isolated from Taiwan to amphotericin B and fluconazole. Prospective surveillance study. Each hospital was asked to submit up to 10 C. albicans and 40 non-albicans Candida species during the collection period, from April 15 to June 15, 1999. One isolate was accepted from each episode of infection. The broth microdilution method was used to determine susceptibilities to amphotericin B and fluconazole. Only 3 of 632 isolates, one each of C. famata, C. krusei, and C. tropicalis, were resistant to amphotericin B. A total of 53 (8.4%) of 632 clinical yeast isolates, consisting of 4% C. albicans, 8% C. glabrata, 15% C. tropicalis, and 70% C. krusei, were resistant to fluconazole. In contrast, no C. parapsilosis isolate was resistant to fluconazole. Isolates from tertiary-care medical centers had higher rates of resistance to fluconazole than did those from regional and local hospitals (11.4% vs 6.6%). Isolates from different sources show...

Journal of microbiology, immunology, and infection = Wei mian yu gan ran za zhi, 2003

From April 15 to June 15, 1999, 581 clinical Candida isolates from 19 hospitals in Taiwan were co... more From April 15 to June 15, 1999, 581 clinical Candida isolates from 19 hospitals in Taiwan were collected and susceptibilities to fluconazole of these isolates were determined by a broth microdilution method. A total of 42 (7.2%) isolates were resistant to fluconazole. Isolates from medical centers had a higher resistance rate to fluconazole than those from regional hospitals (10.7% vs 4.9%). Candida species isolated from different regions had different degrees of susceptibility to fluconazole. Approximately 2.5%, 6.5%, and 11.8% of Candida isolates from middle, north, and south regions, respectively, were resistant to fluconazole. The prevalence of the combination of Candida glabrata, Candida krusei, and Candida tropicalis infections were 44.5%, 49.8%, and 62.7% in middle, north, and south regions, respectively. There is an association between the rate of fluconazole resistance and the number of non-albicans Candida species collected from different regions and hospital types.

PLoS ONE, 2007

Limited structural information of drug targets, cellular toxicity possessed by lead compounds, an... more Limited structural information of drug targets, cellular toxicity possessed by lead compounds, and large amounts of potential leads are the major issues facing the design-oriented approach of discovering new leads. In an attempt to tackle these issues, we have developed a process of virtual screening based on the observation that conformational rearrangements of the dengue virus envelope protein are essential for the mediation of viral entry into host cells via membrane fusion. Screening was based solely on the structural information of the Dengue virus envelope protein and was focused on a target site that is presumably important for the conformational rearrangements necessary for viral entry. To circumvent the issue of lead compound toxicity, we performed screening based on molecular docking using structural databases of medical compounds. To enhance the identification of hits, we further categorized and selected candidates according to their novel structural characteristics. Finally, the selected candidates were subjected to a biological validation assay to assess inhibition of Dengue virus propagation in mammalian host cells using a plaque formation assay. Among the 10 compounds examined, rolitetracycline and doxycycline significantly inhibited plaque formation, demonstrating their inhibitory effect on dengue virus propagation. Both compounds were tetracycline derivatives with IC 50 s estimated to be 67.1 mM and 55.6 mM, respectively. Their docked conformations displayed common hydrophobic interactions with critical residues that affected membrane fusion during viral entry. These interactions will therefore position the tetracyclic ring moieties of both inhibitors to bind firmly to the target and, subsequently, disrupt conformational rearrangement and block viral entry. This process can be applied to other drug targets in which conformational rearrangement is critical to function.

2001 Conference Proceedings of the 23rd Annual International Conference of the IEEE Engineering in Medicine and Biology Society, 2001

Pulsed-field Gel Electrophoresis (PFGE) is an important tool in genomic analysis. The result of P... more Pulsed-field Gel Electrophoresis (PFGE) is an important tool in genomic analysis. The result of PFGE is presented in an image. Each image contains several lanes. And each lane consists of bands. Two lanes are identical if the relative positions of bands are the same. We present a method that uses computer to extract the lanes and compare the lanes in the electrophoresis images. The presented method consists of two major steps. The first step is image processing and lane extraction. The second step is to convert a lane into chain code representation. The lane comparison is carried out through calculating the longest common subsequence between lanes. We define the distance between lanes in term of the LCS and the lengths of two lanes. Two lanes have smaller distance tend to have similar pattern. This method eliminates those very different patterns to help biologists reduce the lanes that need to be compared.

In the past decades, the prevalence of candidemia has increased significantly and drug resistance... more In the past decades, the prevalence of candidemia has increased significantly and drug resistance has also become a pressing problem. Overexpression of CDR1, an efflux pump, has been proposed as a major mechanism contributing to the drug resistance in Candida albicans. It has been demonstrated that biological fluids such as human serum can have profound effects on antifungal pharmacodynamics. The aim of this study is to understand the effects of serum in drug susceptibility via monitoring the activity of CDR1 promoter of C. albicans.

Current Drug Target -Infectious Disorders, 2004

Klebsiella are well-recognized community and nosocomial pathogens responsible for septicemias, ur... more Klebsiella are well-recognized community and nosocomial pathogens responsible for septicemias, urinary tract infections, pneumonia, and soft tissue infections. The emergence of multi-drug resistant Klebsiella is becoming a global concern. Since fluoroquinolones are excellent antibiotics for clinical therapy of complicated infections, their consumptions have increased rapidly. Coincidental with the increased usage of fluoroquinolones, the incidences of drug resistance have increased, which highlights the need for understanding the molecular mechanisms of fluoroquinolone resistance. Alterations in targets and reduction of intracellular drug accumulation are two major mechanisms involved in fluoroquinolone resistance. This review focuses on the mechanisms of action of fluoroquinolones and molecular mechanisms of drug resistance, including known and proposed ones, and the discussion on clinical impact of multi-drug resistance in Klebsiella.

Journal of clinical microbiology, 2010

Among 234 isolates comprising 26 different Candida species colonizing the oropharynx of 181 (54.3... more Among 234 isolates comprising 26 different Candida species colonizing the oropharynx of 181 (54.3% of 399 surveyed) HIV-infected outpatients, 27 (11.7%) were fluconazole resistant. Antibacterial treatment was associated with increased rates of yeast colonization, while antiretroviral therapy and pneumococcal vaccination protected patients from yeast colonization.

Diagnostic microbiology and infectious disease, 2013

Susceptibilities to antifungal drugs of 1083 Candida isolates collected in Taiwan Surveillance of... more Susceptibilities to antifungal drugs of 1083 Candida isolates collected in Taiwan Surveillance of Antimicrobial Resistance of Yeasts in 2010 were determined. There were 422 (39%) C. albicans, 270 (24.9%) C. tropicalis, 258 (23.8%) C. glabrata, 87 (8%) C. parapsilosis, 18 (1.7%) C. krusei, and 28 (2.6%) of 13 other species. In the present study, we have applied species-specific clinical breakpoints for common species and epidemiological cutoff values for rare species. We found that majority of isolates were susceptible to tested drugs. A total of 15, 3, 2, and 0 isolates were not susceptible to fluconazole, voriconazole, amphotericin B, and anidulafungin, respectively. We found that three of the four fluconazole non-susceptible C. albicans isolates were resistant to voriconazole. Hence, there is an issue of cross-resistance among azole-type drugs.

Genomics, 1999

We describe here a novel member of the slow-kinetics immediate-early gene family.Ier5is an intron... more We describe here a novel member of the slow-kinetics immediate-early gene family.Ier5is an intronless gene, encoding a serum- and growth factor-inducible message of 2123 nucleotides that is present in a wide variety of tissues. The predicted open reading frame encodes a 308-amino-acid, highly proline-rich protein with homology to the amino terminus of the immediate-early gene pip92/Ier2/ETR101. Ier5 is predicted to

Background: Among the 162, 244, and 246 Candida tropicalis isolates collected in Taiwan Surveilla... more Background: Among the 162, 244, and 246 Candida tropicalis isolates collected in Taiwan Surveillance of Antimicrobial Resistance of Yeasts (TSARY) in 1999, 2002, and 2006, 23 (14.2%), 0, and 132 (53.7%) isolates with minimum inhibitory concentrations (MICs) of fluconazole ≥ 64 μg/ml, respectively. Methods: Multilocus sequence typing (MLST) was used to characterize the genetic profiles of 102 C. tropicalis isolates collected from 19 hospitals in Taiwan. Results: Among 61 differentiated DSTs, 11 had more than one isolates. Among 53 isolates with MICs ≥ 64 μg/ml, 36 (69.7%) belonged to these 11 types whereas, only 16 (32.7%) ones with MICs ≤ 16 μg/ml did (p=0.005). Furthermore, 24 (45.3%) with MICs ≥ 64 μg/ml belonged to two closely related DSTs (140 and 98) whereas, only 4 (8.2%) ones with MICs ≤ 16 μg/ml did (p=0.00008). Conclusions: Thus, two related DSTs of C. tropicalis isolates with less susceptibility to fluconazole were dominant in Taiwan from 1999 to 2006.

Journal of microbiology, immunology, and infection = Wei mian yu gan ran za zhi

During the past decade, yeast infections have had an important role in nosocomial infections due ... more During the past decade, yeast infections have had an important role in nosocomial infections due to alterations in the immune status of patients. Coincidentally with the increased usage of antifungal agents, the number of reports of drug resistance has increased, which highlights the need for understanding the molecular mechanisms of antifungal agent resistance. This review describes the mechanisms of action of antifungal agents, cellular factors contributing to drug resistance, the known molecular mechanisms of drug resistance, and proposed but unproved molecular mechanisms of drug resistance. This review also proposes possible strategies for preventing drug resistance.

Background: Progressive cell-mediated immunodeficiency with decrease of CD4+ lymphocyte count to ... more Background: Progressive cell-mediated immunodeficiency with decrease of CD4+ lymphocyte count to less than or equal to 200 cells/mm 3 is a major risk factor for colonization with Candida species and development of candidiasis. Oropharyngeal candidiasis may occur in up to 90% of human immunodeficiency virus (HIV)-infected patients during the course of the disease. This study is to determine the effect of prolonged highly active antiretroviral therapy (HAART) on oropharyngeal colonization with Candida species and oral candidiasis.

Journal of Microbiology, 2013

We previously showed that the expression of ENO1 (enolase) in the fungal pathogen Candida albican... more We previously showed that the expression of ENO1 (enolase) in the fungal pathogen Candida albicans is critical for cell growth. In this study, we investigate the contribution of the ENO1 gene to virulence. We conducted our functional study of ENO1 in C. albicans by constructing an eno1/eno1 null mutant strain in which both ENO1 alleles in the genome were knockouted with the SAT1 flipper cassette that contains the nourseothricin-resistance marker. Although the null mutant failed to grow on synthetic media containing glucose, it was capable of growth on media containing yeast extract, peptone, and non-fermentable carbon sources. The null mutant was more susceptible to certain antifungal drugs. It also exhibited defective hyphal formation, and was avirulent in BALB/c mice.

Nanotechnology, 2009

Dengue virus (DENV) is nowadays the most important arthropod-spread virus affecting humans existi... more Dengue virus (DENV) is nowadays the most important arthropod-spread virus affecting humans existing in more than 100 countries worldwide. A rapid and sensitive detection method for the early diagnosis of infectious dengue virus urgently needs to be developed. In the present study, a circulating-flow quartz crystal microbalance (QCM) biosensing method combining oligonucleotide-functionalized gold nanoparticles (i.e. AuNP probes) used to detect DENV has been established. In the DNA-QCM method, two kinds of specific AuNP probes were linked by the target sequences onto the QCM chip to amplify the detection signal, i.e. oscillatory frequency change (DeltaF) of the QCM sensor. The target sequences amplified from the DENV genome act as a bridge for the layer-by-layer AuNP probes&amp;amp;amp;amp;amp;amp;amp;#39; hybridization in the method. Besides being amplifiers of the detection signal, the specific AuNP probes used in the DNA-QCM method also play the role of verifiers to specifically recognize their target sequences in the detection. The effect of four AuNP sizes on the layer-by-layer hybridization has been evaluated and it is found that 13 nm AuNPs collocated with 13 nm AuNPs showed the best hybridization efficiency. According to the nanoparticle application, the DNA-QCM biosensing method was able to detect dengue viral RNA in virus-contaminated serum as plaque titers being 2 PFU ml(-1) and a linear correlation (R(2) = 0.987) of DeltaF versus virus titration from 2 x 10(0) to 2 x 10(6) PFU ml(-1) was found. The sensitivity and specificity of the present DNA-QCM method with nanoparticle technology showed it to be comparable to the fluorescent real-time PCR methods. Moreover, the method described herein was shown to not require expensive equipment, was label-free and highly sensitive.

Mycopathologia, 2011

The opportunistic Candida species existing as part of commensal microbiota in humans are usually ... more The opportunistic Candida species existing as part of commensal microbiota in humans are usually the etiological agents causing infections. We investigated whether isolates collected from different age groups, hospital units, and sources have distinct characteristics. A total of 913 isolates comprising 395 Candida albicans, 230 Candida tropicalis, 202 Candida glabrata, 62 Candida parapsilosis, 13 Candida krusei, and 11 of other six species were analyzed. Urine was the most common source (41.2%), followed by sputum (16.3%), blood (15.2%), and others (27.3%). Candida albicans and C. parapsilosis were more prevalent in the working group [from 19 to 65 years], whereas C. tropicalis and C. glabrata were more prevalent in the elder one (≥ 66 years). We found that the age of patients and the source of isolates affect the distribution of species. On the other hand, the drug susceptibility of isolates was associated with fungal species and whether patients were hospitalized.

Microbial Drug Resistance, 2009

Recently, we reported that diploid sequence type (DST) 140 was a predominant type of Candida trop... more Recently, we reported that diploid sequence type (DST) 140 was a predominant type of Candida tropicalis among isolates with fluconazole minimum inhibitory concentrations (MICs) &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;or=64 microg/ml collected in the Taiwan Surveillance of Antimicrobial Resistance of Yeasts (TSARY) in 1999. To determine if DST140 persists in Taiwan, we have used multilocus sequence typing to characterize the genetic profiles of 31 resistant isolates (MICs &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;or=64 microg/ml), together with 19 susceptible isolates (MICs &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;or=16 microg/ml) collected in TSARY 2006. Among the 50 isolates, 33 distinct DSTs were detected. Of the 31 resistant isolates, 11 (35.5%) belonged to two closely related DSTs (140 and 98), whereas none of the 19 susceptible isolates did (p = 0.004). The isolates belonging to DST140 and 98 were from different geographic regions instead of a restricted area. Thus, our data show temporal and spatial transmission of C. tropicalis clones with high fluconazole MICs in Taiwan from 1999 to 2006.