Biology subjects

Liu, J. L.

Publications and source records attributed to Liu, J. L..

3 recordsLinked to original sources

bioRxiv2025

Contributions of β-lactamase substrate specificity and outer membrane permeability to the antibiotic sheltering of β-lactam-susceptible bacteria

The use of {beta}-lactam antibiotics is threatened by antibiotic resistant bacteria that produce {beta}-lactamases. These enzymes not only protect the bacteria that produce them but also shelter other bacteria in the same environment that would otherwise be susceptible. While this phenomenon is of clinical significance, many of the factors that contribute to {beta}-lactamase-mediated antibiotic sheltering have not been well-studied. We report the development of a luminescence assay to directly monitor the survival of {beta}-lactam-susceptible bacteria in the presence of {beta}-lactamase-producing bacteria and {beta}-lactam antibiotics. This method provides a rapid and scalable means of quantifying antibiotic sheltering in mixed microbial populations. We applied this assay to investigate the contributions of several factors to sheltering, including the class of {beta}-lactam, the substrate specificity of the {beta}-lactamase, and the cell wall permeability of the {beta}-lactamase-producing bacterium. Our results show that the extent of sheltering that occurs depends greatly on the particular combination of {beta}-lactam and {beta}-lactamase, and also on the ability of a {beta}-lactamase to access its {beta}-lactam substrate.

microbiology↗

bioRxiv2025

Rapid Detection of Carbapenemase-Producing Organisms Using a Luminescent Biosensor

Carbapenemase-producing organisms (CPOs) pose an urgent global health threat due to their ability to inactivate carbapenems, a group of last resort antibiotics. Infections caused by these pathogens are associated with poor patient outcomes, high mortality rates, and added burden to infection prevention and control programs, making early detection vital to ensure optimal antimicrobial therapy and appropriate implementation of infection control practices. In this study, we report the application of a luminescent whole-cell biosensor for the rapid detection of CPOs. This biosensor provides positive test results within 2.5 hours, inclusive of setup time, and has been validated with a panel of laboratory and clinical isolates producing a diverse range of carbapenemases (KPC, NDM, IMP, VIM and OXA-48-like). The assay successfully identified all CPO isolates tested with a sensitivity of 100%, including strains producing weak OXA-48-like carbapenemases which are sometimes missed by currently used detection methods. The assay also demonstrated a specificity of 100 %, with all non-CPO clinical isolates testing negative under the optimized assay conditions. Due to the rapid time-to-positivity, minimal setup requirements, and high sensitivity, this test could serve as an attractive alternative to CPO detection methods currently employed by clinical microbiology labs, and could also facilitate CPO screening in other settings (e.g., environmental, agricultural).

microbiology↗

bioRxiv2021

Forward genetics combined with unsupervised classifications identified zebrafish mutants affecting biliary system formation.

Impaired formation of the biliary network can lead to congenital cholestatic liver diseases; however, the genes responsible for proper biliary system formation and maintenance have not been fully identified. Combining computational network structure analysis algorithms with a zebrafish forward genetic screen, we identified 24 new zebrafish mutants that display impaired intrahepatic biliary network formation. Complementation tests suggested that these 24 mutants affect 24 different genes. We applied unsupervised clustering algorithms to classify the recovered mutants into three classes unbiasedly. Further computational analyses revealed that each of the recovered mutations in these three classes shows a unique effect on node subtype composition and connection property distribution of the intrahepatic biliary network. Besides, we found that most recovered mutations are viable. In those mutant fish, biliary network phenotypes persist into adulthood, which themselves are good animal models to study chronic cholestatic liver diseases. Altogether, this study provides unique genetic and computational toolsets that advance our understanding of the molecular pathways leading to biliary system malformation and cholestatic liver diseases.

genetics↗