Biology subjects

Poon, R.

Publications and source records attributed to Poon, R..

5 recordsLinked to original sources

bioRxiv2026

Loss of GdpP function in Staphylococcus aureus confers β-lactam-specific antibiotic tolerance and promotes invasive infection

The emergence of antibiotic tolerance in Staphylococcus aureus reduces antibiotic efficacy by allowing bacterial survival despite prolonged antibiotic exposure, the molecular basis of which remains poorly understood. Moreover, the phenotypic indistinguishability of tolerant isolates in antimicrobial susceptibility testing impedes effective diagnosis and therapy. Increased concentration of the second-messenger, cyclic-di-AMP (CDA), has recently been implicated in tolerance to {beta}-lactams as well as other cell-wall-reactive antibiotics. Using the ScanLag assay, Tolerance-Disk test, and traditional methodologies and employing isogenic mutagenized strains, we demonstrate that loss of GdpP function, a phosphodiesterase that hydrolyzes CDA, confers tolerance specifically to {beta}-lactam antibiotics independent of their class. The extent of {beta}-lactam tolerance correlated directly with the intracellular CDA concentration and inversely with the inhibition of bacterial cell-wall synthesis. {Delta}gdpP mutants caused higher mortality than wild-type strains in the Galleria mellonella infection model upon {beta}-lactam treatment, suggesting GdpP-mediated tolerance could lead to {beta}-lactam treatment failure. Large-scale within-host evolution analysis demonstrated that MRSA and MSSA strains isolated from patients acquire GdpP loss-of-function mutations during invasive infections but not during nasal carriage. Overall, this study highlights the clinical relevance of gdpP mutations, frequently selected in persistent S. aureus infections, as key mediators that could promote treatment failure due to {beta}-lactam tolerance.

microbiology↗

bioRxiv2026

Emergent particle collection by cyanobacteria through gliding motility and filament buckling

Cyanobacterial macrostructures such as mats, aggregates, and stromatolites are observed in diverse habitats. These structures incorporate organic and inorganic matter and form microenvironments enabling biochemical transformations. Macrostructures are found to be associated with motile, filamentous cyanobacteria, but to what extent, and how filament motility can drive macrostructure formation is unclear. To address this question, we study macrostructure formation in a well-characterised freshwater cyanobacterial community dominated by the filamentous cyanobacterium Fluctiforma draycotensis. We discover an emergent particle collection behaviour that results in aggregate macrostructures composed of a solid core surrounded by an outer layer dominated by entangled cyanobacterial filaments. We show that the particle collection and subsequent aggregate formation result from the gliding motility of the cyanobacteria. Developing a novel 3D model of active filament movement, we analyse how filament morphology and mechanical properties affect movement dynamics, particle collection, and filament entanglement. We predict that particle collection requires filaments above a certain length and flexibility. We confirm the resulting prediction of length dependence of particle collection behavior with shortened filaments of F. draycotensis and naturally short Pseudanabaena sp. filaments. Together, our results show that filamentous cyanobacteria can use gliding motility to actively engineer their environments through particle collection and macrostructure formation, and that this ability is confined to a part of the filament phase space in terms of length and flexibility. These insights will allow better prediction of macrostructure formation in natural habitats and specific cyanobacterial species, and the engineering of cyanobacterial macrostructures for biotechnological applications.

biophysics↗

bioRxiv2025

A scotophobic response characterised by body contraction and ciliary arrest in Acropora coral larvae

Planulae of the reef-building coral Acropora millepora exhibit whole-body contraction and ciliary arrest after exposure to sudden light dimming. Quantitative behavioural assays confirmed reductions in swimming speed and alterations in vertical and horizontal movement under alternating light and dark conditions. High-speed microscopy revealed that ciliary activity ceases upon dimming, while the typically elongated body contracts into a rounded form, altering swimming behaviour. These larval responses suggest an adaptive mechanism to regulate positioning within the highly structured and complex light environment of reef habitats, critical for coral recruitment and survival.

neuroscience↗

bioRxiv2022

In-vivo detection of cyclic-di-AMP in Staphylococcus aureus

Cyclic-di-AMP (CDA) is a signaling molecule that controls various cellular functions including antibiotic tolerance and osmoregulation in Staphylococcus aureus. In this study, we developed a novel biosensor (bsuO P6-4) for in-vivo detection of CDA in S. aureus. Our study showed that bsuO P6-4 could detect a wide concentration range of CDA in both laboratory and clinical strains making it suitable for use in both basic and clinical research applications.

microbiology↗

bioRxiv2021

Loss of GdpP function in Staphylococcus aureus leads to β-lactam tolerance and enhanced evolution of β-lactam resistance

SynopsisO_ST_ABSBackgroundC_ST_ABSWe previously reported the presence of mutations in gdpP among Staphylococcus aureus strains that were obtained by serial passaging in {beta}-lactam drugs. gdpP codes for a phosphodiesterase that cleaves cyclic-di-AMP (CDA), a newly discovered second messenger. ObjectivesWe sought to identify the role of gdpP in {beta}-lactam resistance of S. aureus. MethodsCDA concentrations in bacterial cytosol were measured through mass-spectrometric analysis. gdpP deletion mutagenesis and their complemented strains were created in clinically relevant S. aureus strains to characterize its function. ResultsgdpP associated mutations among passaged strains were identified to cause loss of phosphodiesterase function, leading to increased CDA accumulation in the bacterial cytosol. Deletion of gdpP led to an enhanced ability of the bacteria to withstand a {beta}-lactam challenge (two to three log increase in bacterial colony forming units) by promoting tolerance without enhancing MICs of {beta}-lactam antibiotics. Our results demonstrate that increased drug tolerance due to loss of GdpP function can provide a selective advantage in acquisition of high-level {beta}-lactam resistance and could lead to {beta}-lactam treatment failure of S. aureus infections. ConclusionsLoss of GdpP function increases tolerance to {beta}-lactams that can lead to its therapy failure and can permit {beta}-lactam resistance to occur more readily.

microbiology↗