Biology subjects

Heron, R.

Publications and source records attributed to Heron, R..

3 recordsLinked to original sources

bioRxiv2026

Intestinal bacteria hijack an evolutionarily conserved epithelial repair signal

Apoptosis in the gut triggers an expansion in the Enterobacteriaceae family of bacteria, causing both prolonged tissue injury and delayed repair. However, the mechanisms linking the Enterobacteriaceae bloom and subsequent deleterious tissue response are relatively unknown. Here, we establish purines as a major component of the apoptotic secretome that are consumed by bacteria. Explicitly, we identify hypoxanthine as a critical metabolite that is taken up and metabolised by both pathogenic and commensal species within the Enterobacteriaceae family. Epithelial cells release hypoxanthine into the extracellular space during early stages of apoptosis via the upregulation of equilibrative nucleoside transporters 1/2 (ENT1/2). Critically, beyond simply linking host and microbe, we delineate a connection between the release of hypoxanthine from the dying cell and the ability of the host to repair damaged epithelial tissue. Hypoxanthine is a potent promoter of epithelial cell repair in both gut and skin across the phylogenetic tree including humans, mice, zebrafish, and fruit flies and promotes similar ATP production and cellular proliferation in eukaryotic and microbial recipients. Thus, the preferential utilisation of hypoxanthine by the Enterobacteriaceae directly competes with the host for a core reparative signal.

microbiology↗

bioRxiv2026

Nuclear plasticity regulates macrophage phagocytic capacity in vivo

Macrophages fine-tune their appetite to fulfil their clearance role, but how they achieve this is incompletely understood. The nucleus can sense and respond to extracellular physical challenges, but whether it can also detect and react to intracellular mechanical inputs is unclear. Here, we tested the hypothesis that phagosomes exert a strain on the nucleus, and that the consequent nuclear mechanoresponse influences macrophage appetite. Combining genetic manipulation and live in vivo imaging, we show that engulfed apoptotic bodies indent the nucleus of Drosophila embryonic macrophages, leading to nuclear deformation and causing an increase in Lamin B levels. We demonstrate that these phagosome-induced nuclear molecular and mechanical adaptations are critical for macrophages to sustain uptake - unveiling a role for nuclear plasticity in the regulation of macrophage phagocytic capacity in vivo.

cell biology↗

bioRxiv2020

Mfd affects global transcription and the physiology of stressed Bacillus subtilis cells

For several decades, Mfd has been studied as the bacterial transcription-coupled repair factor. However, recent observations indicate that this factor influences cell functions beyond DNA repair. Our lab recently described a role for Mfd in disulfide stress that was independent of its function in nucleotide excision repair and base excision repair. Because reports showed that Mfd influenced transcription of single genes, we investigated the global differences in transcription in wild-type and mfd mutant growth-limited cells in the presence and absence of diamide. Surprisingly, we found 1,997 genes differentially expressed in Mfd- cells in the absence of diamide. Using gene knockouts, we investigated the effect of genetic interactions between Mfd and the genes in its regulon on the response to disulfide stress. Interestingly, we found that Mfd interactions were complex and identified additive, epistatic, and suppressor effects in the response to disulfide stress. Pathway enrichment analysis of our RNASeq assay indicated that major biological functions, including translation, endospore formation, pyrimidine metabolism, and motility, were affected by the loss of Mfd. Further, our RNASeq findings correlated with phenotypic changes in growth in minimal media, motility, and sensitivity to antibiotics that target the cell envelope, transcription, and DNA replication. Our results suggest that Mfd has profound effects on the modulation of the transcriptome and on bacterial physiology, particularly in cells experiencing nutritional and oxidative stress.

microbiology↗