Biology subjects

Liao, Y.-S.

Publications and source records attributed to Liao, Y.-S..

3 recordsLinked to original sources

bioRxiv2026

Evaluation of Oxford Nanopore Sequencing for Antimicrobial Resistance Surveillance in Salmonella: Comparison with Phenotypic Antimicrobial Susceptibility in a Large-Scale Study

Salmonella is a major zoonotic foodborne pathogen, and antimicrobial resistance (AMR) in Salmonella presents a significant public health challenge. Whole-genome sequencing (WGS) offers a more rapid and comprehensive method for AMR characterization compared to conventional antimicrobial susceptibility testing (AST), supporting antimicrobial therapy and surveillance efforts. In this study, Oxford Nanopore Technology (ONT)-based WGS was performed on 1,490 Salmonella isolates collected through nationwide surveillance in Taiwan in 2025. Genotypic resistance inferred from WGS data was compared with phenotypic AST results to assess the performance of ONT-WGS. Overall, WGS-inferred resistance showed high concordance with phenotypic resistance for most antimicrobials. However, major genotype- phenotype discordance was observed, attributed to four categories: (i) breakpoint-dependent classification, (ii) reduced or absent phenotypic expression of resistance genes, (iii) MIC modulation by ramAp, and (iv) absence of known AMR determinants. Notable discrepancies included tigecycline resistance without known genetic determinants, nalidixic acid resistance linked to ramAp-mediated MIC elevation, and a high prevalence of colistin resistance (35.4%) in S. Enteritidis without identifiable AMR determinants. Additionally, a significant proportion of ESBL- and AmpC-producing isolates were classified as susceptible or intermediate to cefotaxime and ceftazidime under CLSI criteria, highlighting the potential for misclassification and treatment failure. These findings demonstrate that ONT-WGS enables accurate, comprehensive AMR characterization, offering direct identification of AMR determinants and minimizing misclassification due to breakpoint-based AST interpretations. When interpreted appropriately, WGS can support better antimicrobial selection and serve as a valuable alternative to conventional susceptibility testing.

microbiology↗

bioRxiv2020

Modulation of Transient receptor potential melastatin 3 by protons through its intracellular binding sites

Transient receptor potential melastatin 3 channel (TRPM3) is a calcium-permeable nonselective cation channel that plays an important role in modulating glucose homeostasis in the pancreatic beta cells. However, how TRPM3 is regulated under physiological and pathological conditions is poorly understood. In this study, we found that both intracellular and extracellular protons block TRPM3 through its intracellular binding sites. We demonstrated that external protons indirectly block TRPM3, whereas internal protons inhibit TRPM3 directly with an inhibitory pH50 of 6.9 {+/-} 0.11. We identified three titratable residues, D1059, D1062, and D1073, at the inner vestibule of the channel pore that contribute to pH sensitivity. The mutation of D1073Q reduces TRPM3 current intensity and pH sensitivity; Replacement of Asp 1073 by Gln 1073 changes the reduction of TRPM3 outward current by low external pH 5.5, from 62 {+/-} 3 % in WT to 25 {+/-} 6.0 % in D1073Q. These results indicate that D1073 is not only essential for intracellular pH sensitivity, but it is also crucial for TRPM3 channel gating. In addition, a single mutation of D1059 or D1062 enhances pH sensitivity. In summary, our findings provide a novel molecular determinant for pH regulation of TRPM3. The inhibition of TRPM3 by protons may indicate an endogenous mechanism governing TRPM3 gating and its physiological/ pathological functions.

pharmacology and toxicology↗

bioRxiv2020

Identification of 2019-nCoV related coronaviruses in Malayan pangolins in southern China

The ongoing outbreak of viral pneumonia in China and beyond is associated with a novel coronavirus, provisionally termed 2019-nCoV. This outbreak has been tentatively associated with a seafood market in Wuhan, China, where the sale of wild animals may be the source of zoonotic infection. Although bats are likely reservoir hosts for 2019-nCoV, the identity of any intermediate host facilitating transfer to humans is unknown. Here, we report the identification of 2019-nCoV related coronaviruses in pangolins (Manis javanica) seized in anti-smuggling operations in southern China. Metagenomic sequencing identified pangolin associated CoVs that belong to two sub-lineages of 2019-nCoV related coronaviruses, including one very closely related to 2019-nCoV in the receptor-binding domain. The discovery of multiple lineages of pangolin coronavirus and their similarity to 2019-nCoV suggests that pangolins should be considered as possible intermediate hosts for this novel human virus and should be removed from wet markets to prevent zoonotic transmission.

microbiology↗