Biology subjects

Greer, B.

Publications and source records attributed to Greer, B..

3 recordsLinked to original sources

bioRxiv2025

Struvite fertiliser offers a sustainable solution for recycling of phosphorus for crop growth without altering the soil resistome.

BackgroundThe reserves of rock phosphate, used to produce fertilisers, are being exhausted by the ever-increasing pressure to meet the food demands of a growing world population. Sustainable alternatives are urgently needed, and struvite, a renewable phosphorus fertiliser recovered from waste streams such as animal manure, offers a promising solution. However, other manure-derived fertilisers have been associated with the promotion of antimicrobial resistance (AMR) in soil, raising concerns about whether struvite might pose similar risks. Despite this, the impact of struvite on the soil resistome remains poorly understood. MethodsThis study assesses the AMR risk associated with Xiamen struvite (XIA), produced from piggery wastewater, compared with two commercial fertilisers: Crystal Green (CG) and Triple Super Phosphate (TSP), and an untreated control soil. Following a three-month fertilisation period, rhizospheric soils were analysed using mass spectrometry to investigate antimicrobial residues in the soil, and shotgun metagenomics and culture-based assays, and bacterial isolate characterisation to identify bacterial AMR linked to the treatments. Notably, this is the first study to apply culturing methods to investigate struvites impact on AMR. Results and conclusionsWhile XIA struvite soil fertilisation led to an increase in total culturable bacterial load, (CFU/g), there was no evidence of antimicrobial residues detected in soil, as confirmed by mass spectrometry. Metagenomic profiling further revealed no significant alterations to antimicrobial resistance genes (ARGs) across all treatments, including CG, TSP, and untreated controls. Culture-based analysis supported these findings, with tetracycline-resistant bacteria undetected and only minimal resistance observed to erythromycin, florfenicol, and neomycin. Although resistance levels to amoxicillin, streptomycin, and trimethoprim were higher in XIA-treated soils, this appeared to reflect a broader increase in microbial load rather than selective enrichment of resistant strains. These data suggest that piggery-derived struvite does not impose a clear AMR risk in soil and performs similarly to conventional fertilisers. While it appears to increase total bacterial load, there is no evidence of selective enrichment for AMR bacteria. However, variability in antimicrobial and ARG content across studies highlights the need for standardised production specifications for struvites to ensure safety and consistency. This study provides the most comprehensive assessment to date of struvites AMR implications, supporting its potential as a safe, sustainable fertiliser and contributing valuable insights to inform regulatory guidance.

microbiology↗

bioRxiv2024

Mitochondrial metabolism is a key determinant of chemotherapy sensitivity in Colorectal Cancer

Therapy resistance is attributed to over 80% of cancer deaths per year emphasizing the urgent need to overcome this challenge for improved patient outcomes. Despite its widespread use in colorectal cancer (CRC) treatment, resistance to 5-fluorouracil (5FU) remains poorly understood. Here, we investigate the transcriptional responses of CRC cells to 5FU treatment, revealing significant metabolic reprogramming towards heightened mitochondrial activity. Utilizing CRC models, we demonstrate sustained enhancement of mitochondrial biogenesis and function following 5FU treatment, leading to resistance in both in vitro and in vivo settings. Furthermore, we show that targeting mitochondrial metabolism, specifically by inhibiting Complex I (CI), sensitizes CRC cells to 5FU, resulting in delayed tumour growth and prolonged survival in preclinical models. Additionally, our analysis of patient data suggests that oxidative metabolism signatures may predict responses to 5FU-based chemotherapy. These findings shed light on mechanisms underlying 5FU resistance and propose a rational strategy for combination therapy in CRC, emphasizing the potential clinical benefit of targeting mitochondrial metabolism to overcome resistance and enhance patient outcomes.

cancer biology↗

bioRxiv2020

Extensive proteomic and transcriptomic changes quench the TCR/CD3 activation signal of latently HIV-1 infected T cells

Although the ability of HIV-1 to reside in a latent state in CD4+ T cells constitutes a critical hurdle to a curative therapy, the biomolecular mechanisms by which latent HIV-1 infection is established and maintained are only partially understood. Ex vivo studies have shown that T cell receptor/CD3 stimulation only triggered HIV-1 reactivation in a fraction of the latently infected CD4+ T cell reservoir, suggesting that parts of the T cell population hosting latent HIV-1 infection events are altered to be TCR/CD3-activation-inert. We provide experimental evidence that HIV-1 infection of primary T cells and T cell lines indeed generates a substantial amount of TCR/CD3 activation-inert latently infected T cells. HIV-1 induced host cell TCR/CD3 inertness is thus a conserved mechanism that contributes to the stability of latent HIV-1 infection. Proteomic and genome-wide RNA-level analysis comparing CD3-responsive and CD3-inert latently HIV-1 infected T cells, followed by software-based integration of the data into protein-protein interaction networks (PINs) suggested two phenomena to govern CD3-inertness: (i) the presence of extensive transcriptomic noise that affected the efficacy of CD3 signaling and (ii) defined changes to specific signaling pathways. Validation experiments demonstrated that compounds known to increase transcriptomic noise further diminished the ability of TCR/CD3 stimulation to trigger HIV-1 reactivation. Conversely, targeting specific central nodes in the generated PINs such as STAT3 improved the ability of TCR/CD3 activation to trigger HIV-1 reactivation in T cell lines and primary T cells. The data emphasize that latent HIV-1 infection is largely the result of extensive, stable biomolecular changes to the signaling network of the host T cells harboring latent HIV-1 infection events. In extension, the data imply that therapeutic restoration of host cell TCR/CD3 responsiveness could enable gradual reservoir depletion without the need for therapeutic activators, driven by cognate antigen recognition. AUTHOR SUMMARYA curative therapy for HIV-1 infection will at least require the eradication of a small pool of CD4+ helper T cells in which the virus can persist in a latent state, even after years of successful antiretroviral therapy. It has been assumed that activation of these viral reservoir T cells will also reactivate the latent virus, which is a prerequisite for the destruction of these cells. Remarkably, this is not the case and following application of even the most potent stimuli that activate normal T cells through their T cell receptor, a large portion of the latent virus pool remains in a dormant state. Herein we demonstrate that a large part of latent HIV-1 infection events reside in T cells that have been rendered activation inert by the actual infection event. We provide a systemwide, biomolecular description of the changes that render latently HIV-1 infected T cells activation inert and using this description, devise pharmacologic interference strategies that render initially activation inert T cells responsive to stimulation. This in turn allows for efficient triggering of HIV-1 reactivation in a large part of the latently HIV-1 infected T cell reservoir.

microbiology↗