Biology subjects

Liew, J. H.

Publications and source records attributed to Liew, J. H..

5 recordsLinked to original sources

bioRxiv2026

Layered phage therapy exploits capsule-loss escape and altered antibiotic susceptibility in CG23 hypervirulent Klebsiella pneumoniae

The rise of drug-resistant Klebsiella pneumoniae infections is prompting a re-evaluation of phage therapy as an alternative treatment. Phage therapy has achieved successful outcomes, yet important limitations persist, including the rapid emergence of phage resistance and the time required to source suitable phages. Combining multiple phages into a phage cocktail based on genetic diversity, morphology or distinct infection mechanisms is a common strategy to mitigate resistance. Phage pairing based on these criteria neither mitigates nor delays the emergence of resistance, using CG23 hypervirulent Klebsiella pneumoniae (hvKp) EC0675 as a model. In CG23 Kp strains, resistance arises through disruption of the capsular biosynthetic pathway, leading to capsule impairment and global cross-resistance to all capsule-active phages. Combining phages active against encapsulated wild-type bacteria with those active against capsule-deficient escape mutants can overcome this constraint, improving bacterial suppression in vitro and reducing bacterial burdens across multiple organs in a mouse systemic infection model. In parallel, phage-driven capsule loss increased susceptibility of hvKp EC0675 to selected antibiotics targeting the bacterial envelope or cell wall in vitro. These findings highlight the contribution of capsule-associated resistance to phage cross-resistance in the CG23 Kp strains examined, and support further evaluation of phage combinations targeting both wild-type bacteria and resistant derivatives, including their use alongside selected antibiotics, informing future clinical translation.

microbiology↗

bioRxiv2026

Cryo-electron microscopy structure of Jabs, a bacteriophage infecting the multidrug-resistant pathogen Mycobacterium abscessus

Exploring bacteriophage structural diversity is essential for understanding phage biology and for advancing phage-based therapies. Here, we determine the cryo-electron microscopy structure of Jabs, providing, to our knowledge, the first high-resolution view of a phage infecting the multidrug-resistant human pathogen Mycobacterium abscessus. Although Jabs displays the canonical organization of a siphophage, its virion combines several unusual architectural features. The T=9 icosahedral capsid is assembled from two distinct major capsid proteins, with one forming the hexons and the other the pentons, revealing an unprecedented capsid assembly strategy among icosahedral phages. An extensive network of ~1,700 disulfide bonds stabilize individual structural components and covalently links the capsid, connector, tail, and adhesion device into a continuous assembly. At the distal end of the tail, an elaborate and conformationally dynamic adhesion device comprises multiple candidate receptor-binding proteins organized into complex multidomain architectures, including carbohydrate-binding modules and {beta}-sandwich hetero- and homotrimers resembling the receptor-binding proteins of phages infecting lactic acid bacteria. Together, these findings expand our understanding of phage structural diversity and provide a framework for investigating phage-host interactions and guiding the engineering of therapeutic phages.

microbiology↗

bioRxiv2025

Gelatinase regulates the egress of intracellular replicating populations during Enterococcus faecalis infection

Enterococcus faecalis is a common opportunistic pathogen, frequently isolated from chronic wounds, yet the mechanisms underlying its virulence and persistence in this niche remain incompletely understood. We previously showed that a subpopulation of E. faecalis can survive intracellularly for several days during murine wound infection and can replicate within macrophages, revealing an unexpected intracellular phase for this traditionally extracellular bacterium. Here, we identify the secreted metalloprotease gelatinase (GelE) and its regulator, the Fsr quorum sensing system, as key modulators of E. faecalis intracellular survival and replication. Mechanistically, Fsr quorum sensing is induced during intracellular replication, promoting GelE-dependent host cell lysis and bacterial egress. In the absence of active GelE, E. faecalis accumulates as large intracellular clusters, a phenotype observed consistently across GelE deficient wound isolates. In a mouse wound model, GelE deficient E. faecalis similarly exhibited higher intracellular numbers within wound infection-associated host cells. Together, our study uncovers GelE as a central effector that orchestrates the transition between intracellular and extracellular lifestyles of E. faecalis, providing a possible explanation for its persistence in chronic wound infection. Author summaryPathogenic bacteria are traditionally classified as either "intracellular" or "extracellular", but growing evidence suggests that many extracellular bacteria also adopt transient intracellular lifestyles that promote persistent and recurrent infection. Enterococcus faecalis, a leading cause of chronic wound infection, exemplifies this duality. We discovered that E. faecalis strains lacking the secreted protease gelatinase accumulate to high numbers inside host cells such as macrophages. Our data indicate that gelatinase facilitates bacterial escape following intracellular replication, regulating the transition between an intracellular and extracellular lifestyle. During infection, gelatinase-deficient bacteria remain hidden within various wound cell types, potentially evading immune clearance and antibiotic treatment. This work reveals a previously unrecognized role for gelatinase in controlling E. faecalis intracellular dynamics, highlighting a mechanism that may underline chronic and persistent infection.

microbiology↗

bioRxiv2025

Highlighting the species diversity, pricing trends, and conservation concerns in a major ornamental fish hub

The global ornamental fish trade presents significant challenges to conservation of biodiversity. Here we explore patterns in the freshwater ornamental fish market in Hong Kong, a major wildlife trading hub. Weekly surveys over three-months in the primary aquarium district documented 540 freshwater fish species from 73 families. We found that species occurrence in the market was largely price-driven, and minimum retail price was the strongest predictor of their frequency of occurrence. Along the occurrence-price gradient, we found that potentially undescribed species dominated the rare/expensive end of the market, potentially influenced by the anthropogenic allee effect. Alarmingly, 86 species (16%) were potentially undescribed, while 38% were either not evaluated or classified as Data Deficient by the IUCN. While common/cheaper species dominate the market, the substantial number of little-known species being sold is of conservation concern, underscoring the need for more extensive monitoring at the risk of losing them to unregulated exploitation.

zoology↗

bioRxiv2023

The reference genome of the paradise fish (Macropodus opercularis)

Over the decades, a small number of model species, each representative of a larger taxa, have dominated the field of biological research. Amongst fishes, zebrafish (Danio rerio) has gained popularity over most other species and while their value as a model is well documented, their usefulness is limited in certain fields of research such as behavior. By embracing other, less conventional experimental organisms, opportunities arise to gain broader insights into evolution and development, as well as studying behavioral aspects not available in current popular model systems. The anabantoid paradise fish (Macropodus opercularis), an "air-breather" species from Southeast Asia, has a highly complex behavioral repertoire and has been the subject of many ethological investigations, but lacks genomic resources. Here we report the reference genome assembly of Macropodus opercularis using long-read sequences at 150-fold coverage. The final assembly consisted of {approx}483 Mb on 152 contigs. Within the assembled genome we identified and annotated 20,157 protein coding genes and assigned {approx}90% of them to orthogroups. Completeness analysis showed that 98.5% of the Actinopterygii core gene set (ODB10) was present as a complete ortholog in our reference genome with a further 1.2 % being present in a fragmented form. Additionally, we cloned multiple genes important during early development and using newly developed in situ hybridization protocols, we showed that they have conserved expression patterns.

genomics↗