Biology subjects

McLean, J.

Publications and source records attributed to McLean, J..

7 recordsLinked to original sources

bioRxiv2026

A domesticated prophage enzyme links bacterial metabolism, episymbiosis and phage fitness

Prophages are increasingly recognized as drivers of bacterial adaptation, yet how domesticated prophage genes shape microbial symbiosis remains poorly understood. Here, we identify GDPDXhp1, a glycerophosphodiester phosphodiesterase encoded by prophage Xhp1 of Schaalia odontolytica XH001, as a metabolic regulator linking bacterial physiology, episymbiosis and phage fitness. Association with the epibiotic bacterium Nanosynbacter lyticus TM7x strongly induced gdpdXhp1 expression and triggered GDPDXhp1-dependent lipid droplet accumulation in XH001. GDPDXhp1 orchestrated glycerophospholipid remodeling, membrane biophysical properties, respiration and cell-surface glycan composition in XH001, thereby promoting TM7x episymbiosis. Remarkably, GDPDXhp1 was also required for productive Xhp1 infection by remodeling susceptible bacterial host envelope structures to facilitate phage-host interactions. Together, our findings reveal a domesticated prophage enzyme that contributes to bacterial metabolism, interspecies symbiosis and viral reproduction, highlighting prophage as an overlooked source of metabolic innovation in microbial symbiosis.

microbiology↗

bioRxiv2025

LiDAR and hyperspectral-based structured population models show future forest fire frequency may compromise forest resilience

AbstractForest disturbances are accelerating biodiversity loss and altering tree productivity worldwide. Post-disturbance recovery time is critical for identifying vulnerable areas and targeting conservation but varies with environmental conditions. Monitoring recovery at scale requires tracking tree dynamics, yet traditional ground-based approaches are resource-intensive. We present a pipeline to parameterise integral projection models (IPMs) using LiDAR and hyperspectral data to assess post-fire recovery across large, forested areas. Focusing on the fire-adapted Picea mariana, we model passage times to reproductive heights and life expectancy under different fire regimes as indicators of recovery. To do this, we combined hyperspectral-derived species maps and LiDAR-based crown heights to track individual tree survival and growth at the Caribou-Poker Creek Research Watershed (BONA) from 2017-2023. We incorporated fire history, aspect, slope, elevation, and surrounding canopy height into our models and found partial support for their expected effects on survival and growth. Once accounting for topography and competition, we estimated passage times to reproductive maturity (11-22 years). Life expectancy in the absence of fire is shortest on North-facing slopes with recent fire (579 years). Sensitivity analyses highlight fire history and aspect as key modulators of population resilience, with elevation exerting strong influence on life expectancy across all conditions. Our results demonstrate that remotely sensed IPMs can effectively quantify forest recovery at scale, revealing that in some contexts, stands of P. mariana may not recover between fire disturbances. We discuss the implications of these findings for resilience-based forest management and highlight both the challenges and opportunities of using LiDAR and hyperspectral data to build demographic models for forecasting forest dynamics.

ecology↗

bioRxiv2025

Short-term alterations in dietary amino acids override host genetic susceptibility and reveal mechanisms of Salmonella Typhimurium small intestine colonization

In addition to individual genetics, environmental factors (e.g., dietary changes) may influence host susceptibility to gastrointestinal infection through unknown mechanisms. Herein, we developed a model in which CBA/J mice, a genetically resistant strain that tolerates intestinal colonization by the enteric pathogen Salmonella Typhimurium (S. Tm), rapidly succumb to infection after exposure to a diet rich in L-amino acids (AA). In mice, S. Tm-gastroenteritis is restricted to the large intestine (cecum), limiting their use to understand S. Tm small intestine (ileum) colonization, a feature of human Salmonellosis. Surprisingly, CBA mice fed AA diet developed ileitis with enhanced S. Tm ileal colonization. Using germ-free mice and ileal-fecal slurry transplant, we found diet-mediated S. Tm ileal expansion to be microbiota-dependent. Mechanistically, S. Tm relied on Fructosyl-asparagine utilization to expand in the ileum during infection. We demonstrate how AA diet overrides host genetics by altering the gut microbiotas ability to prevent S. Tm ileal colonization.

microbiology↗

bioRxiv2025

Modelling forest dynamics using integral projection models (IPMs) and repeat LiDAR

O_LIEstimating the life histories and population dynamics of trees is important for predicting how forests respond to climate change and disturbances. To do so, ecologist often use stage-structured population models, which explicitly account for individual heterogeneity. However, the data needed to parameterise these models is typically constrained by time- and labour-intensive field methods. C_LIO_LIDespite growing access to remote sensing imagery that could potentially satiate these data-hungry population models, these data remain underutilised in population ecology. Here, we demonstrate a pipeline that integrates repeat-LiDAR data with a type of structured demographic model (Integral Projection Model, IPM) to examine forest-wide dynamics in response to environmental drivers. Using Australias Great Western Woodlands as a case study, we model the survival and growth of [~]40,000 eucalypt trees over a decade to estimate their life expectancy and characterise multiple stages of growth (height growth and crown expansion). C_LIO_LIOur results indicate distinct responses of small trees (where vital rates are predicted by height) and large trees (which invested predominantly in expanding crown area) to proxies for competition and soil moisture (local canopy density and topographic wetness index, respectively). Parameterising structured population models using LiDAR data therefore offers a step-change in perspective towards more ecologically meaningful forest dynamics. C_LIO_LITo broaden the application of this pipeline, we highlight three priorities: (1) Application to more complex systems such as mixed species stands and dense, multilayered canopies); (2) Incorporating complete life histories, including reproduction and early life stages; and (3) Using in long-term or comparative studies through improved availability of high-quality, comparable, repeat-LiDAR surveys. By combining remote sensing data with detailed insights from field- based studies, this pipeline represents a scalable framework for guiding forest management and conservation decisions. C_LI

ecology↗

bioRxiv2024

CYP3A5 inhibition causes G1/S blockade and synergizes with CDK4/6 inhibitor to suppress prostate cancer cell growth: Implications in reducing health disparity

Prostate cancer (PC) is a leading cause of death in men because of the high incidence and long-term inefficacy of the existing treatment options. Furthermore, it exhibits significant health disparities that affect African-American (AA) men more adversely than others do. Previously, we established CYP3A5, a highly expressed protein in AAs PC, as a positive regulator of androgen receptor (AR) signaling. We examined the impact of CYP3A5 depletion on genome-wide transcriptional output using RNA sequencing to gain deeper mechanistic insights. The data revealed that 561 genes were downregulated and 263 were upregulated upon silencing of CYP3A5 in PC cells. Furthermore, in silico pathway analyses of differentially expressed genes suggested that the cell cycle regulation pathway was most significantly affected by CYP3A5 inhibition. Cell cycle analysis of CYP3A5-silenced cells and those treated with clobetasol, a specific CYP3A5 pharmacological inhibitor, showed G1/S phase blockade. Both CYP3A5-depletion and pharmacological inhibition resulted in the downregulation of cyclin D, cyclin B, and CDK2, along with the upregulation of p27kip1 but had minimal effects on CDK4/6 levels. Combination treatment with clobetasol and the CDK4/6 inhibitor palbociclib exhibited synergy with combination index (CI) values ranging from 0.28-0.78. Our findings support the utility of CYP3A5 as a druggable therapeutic target that works more effectively in combination with CDK4/6 inhibition to limit the progression of PC, especially for AA patients with AA. This combination addresses CDK4/6 inhibitor resistance, which is often linked to CDK2 overexpression, and can potentially be useful in reducing disparities in the clinical outcomes of PC. SignificanceOur study highlights CYP3A5 as a key regulator of the cell cycle in prostate cancer (PC). Its overexpression in African American (AA) patients may be a key molecular driver of disparities in outcomes. The combination of CYP3A5 and CDK4/6 inhibitors shows a synergistic effect on therapeutic outcomes and addresses CDK2-mediated resistance. Thus, targeting both CYP3A5 and CDK4/6 could improve treatment outcomes, especially in AA PC patients.

cancer biology↗

bioRxiv2023

A standard protocol to report discrete stage-structured demographic information

O_LIStage-based demographic methods, such as matrix population models (MPMs), are powerful tools used to address a broad range of fundamental questions in ecology, evolutionary biology, and conservation science. Accordingly, MPMs now exist for over 3,000 species worldwide. These data are being digitised as an ongoing process and periodically released into two large open-access online repositories: the COMPADRE Plant Matrix Database and the COMADRE Animal Matrix Database. During the last decade, data archiving and curation of COMPADRE and COMADRE, and subsequent comparative research, have revealed pronounced variation in how MPMs are parameterized and reported. C_LIO_LIHere, we summarise current issues related to the parameterisation and reporting of MPMs that arise most frequently and outline how they affect MPM construction, analysis, and interpretation. To quantify variation in how MPMs are reported, we present results from a survey identifying key aspects of MPMs that are frequently unreported in manuscripts. We then screen COMPADRE and COMADRE to quantify how often key pieces of information are omitted from manuscripts using MPMs. C_LIO_LIOver 80% of surveyed researchers (n=60) state a clear benefit to adopting more standardised methodologies for reporting MPMs. Furthermore, over 85% of the 300 MPMs assessed from COMPADRE and COMADRE omitted one or more elements that are key to their accurate interpretation. Based on these insights, we identify fundamental issues that can arise from MPM construction and communication and provide suggestions to improve clarity, reproducibility, and future research utilising MPMs and their required metadata. To fortify reproducibility and empower researchers to take full advantage of their demographic data, we introduce a standardized protocol to present MPMs in publications. This standard is linked to www.compadre-db.org, so that authors wishing to archive their MPMs can do so prior to submission of publications, following examples from other open-access repositories such as DRYAD, Figshare, and Zenodo. C_LIO_LICombining and standardising MPMs parameterized from populations around the globe and across the tree of life opens up powerful research opportunities in evolutionary biology, ecology, and conservation research. However, this potential can only be fully realised by adopting standardised methods to ensure reproducibility. C_LI

ecology↗

bioRxiv2022

Serine Deamination as a New Acid Resistance Mechanism in Escherichia coli

Escherichia coli associates with humans early in life and can occupy several body niches either as a commensal in the gut and vagina, or as a pathogen in the urinary tract. As such, E. coli has an arsenal of acid response mechanisms that allow it to withstand the different levels of acid stress encountered within and outside the host. Here, we report the discovery of an additional acid response mechanism that involves the deamination of L-serine to pyruvate by the conserved L-serine deaminases SdaA and SdaB. L-serine is the first amino acid to be imported in E. coli during growth in laboratory media, as the culture senesces. However, there remains a lack in knowledge as to why L-serine is preferred and how it is utilized. We show that in acidified media, L-serine is brought into the cell via the SdaC transporter and deletion of both SdaA and SdaB renders E. coli susceptible to acid stress, with a phenotype similar to other acid stress deletion mutants. We also show that the pyruvate produced by L-serine de-amination activates the pyruvate sensor BtsS, which in concert with the non-cognate response regulator YpdB upregulates the putative transporter YhjX, similar to what has been reported for this system during transition of E. coli to stationary phase. Based on these observations, we propose that L-serine deamination constitutes another acid response mechanism in E. coli that may function to protect E. coli as it transitions to stationary phase of growth. IMPORTANCEThe observation that L-serine uptake occurs as an E. coli culture senesces is well-established, yet the benefit E. coli garners from this uptake remains unclear. Here, we report a novel acid resistance mechanism, where L-serine is deaminated to pyruvate and ammonia, promoting acid tolerance in E. coli. This study is important as it provides evidence of the use of L-serine as an acid response strategy, not previously reported for E. coli.

microbiology↗