Biology subjects

Manzano, C.

Publications and source records attributed to Manzano, C..

6 recordsLinked to original sources

bioRxiv2026

The intestinal immune response is influenced by nutritional-status and increased physical activity level

Beyond its role in digestion and barrier function, the intestine is an energy-responsive organ that actively regulates molecular metabolism. Whether and how lifestyle interventions regulate intestinal metabolism at both tissue and molecular levels remain unclear. Here, we show that both chronic exercise and dietary energy density drive robust, segment-specific intestinal remodeling. Voluntary wheel running in ad-libitum chow fed mice, induced elongation of the small intestine and colon, alongside pronounced, region-specific, transcriptional changes in the proximal, mid, and distal small intestine, particularly within immune and stress-related pathways. Caloric dilution diet also increased intestinal length in mice but elicited transcriptional adaptations, prominently in the proximal small intestine, directly linking energy density and intake to structural and molecular plasticity. In contrast, voluntary wheel running in control-fed and caloric-diluted-fed mice subtly modulated immune-associated gene expression, highlighting that diet and physical activity induce complementary and mechanistically distinct effects on the gut. We further identified an exercise-induced state of intestinal preconditioning. Upon refeeding, sedentary mice mounted robust, segment-specific activation of apoptotic, proliferative, and immune pathways. Similarly, acute treadmill exercise acted as a transient intestinal stressor in sedentary animals by shortening the length of the small intestine and rapidly activating epithelial stress, apoptosis, proliferation, and immune signaling. However, these responses were attenuated in chronically active mice despite higher basal expression of key genes, consistent with adaptive epithelial remodeling. The results suggest that habitual physical activity buffers acute nutritional stress and restrains excessive intestinal immune activation. Finally, translational plasma analyses in humans demonstrate that acute moderate-intensity exercise increases circulating markers of monocyte activation and epithelial stress, including CD14, IL-32, Reg-3-alpha and I-FABP, in both lean and obese individuals. Collectively, these findings suggest that the intestine plays a role as a metabolic organ that integrates energy-sensing signals from diet composition and physical activity.

immunology↗

bioRxiv2025

Enterococcus faecalis redox metabolism activates the unfolded protein response to impair wound healing

Enterococcus faecalis is an opportunistic pathogen that thrives in biofilm-associated infections and delays wound healing, yet how it impairs host tissue responses is unclear. Here, we identified extracellular electron transport (EET) as a previously unrecognized source of ROS in E. faecalis and show that this activity directly triggers the unfolded protein response (UPR) in epithelial cells and delays epithelial cell migration. ROS detoxification with catalase suppressed E. faecalis-induced UPR and rescued epithelial cell migration, while exogenous H2O2 was sufficient to restore UPR activation in EET-deficient strains. Importantly, UPR disruption by pharmacological inhibition also impaired cell migration, highlighting a critical role for UPR homeostasis in wound repair. Our findings establish EET as a novel virulence mechanism that links bacterial redox metabolism to host cell stress and impaired repair, offering new avenues for therapeutic intervention in chronic infections.

microbiology↗

bioRxiv2025

Fsr quorum sensing system restricts biofilm growth and activates inflammation in enterococcal infective endocarditis

Infective endocarditis (IE) is a life-threatening biofilm-associated infection, yet the factors driving biofilm formation remain poorly understood. Here, we identified the Fsr quorum sensing (QS) system of Enterococcus faecalis as a potent negative regulator of IE pathogenesis. Using microfluidic and in vivo models, we show that Fsr is induced in late IE when bacteria become shielded from blood flow. Deleting Fsr altered biofilm metabolism and promoted robust biofilm growth and gentamicin tolerance in vivo. Furthermore, Fsr inactivation attenuated inflammation by disrupting IL-1{beta} cleavage and activation via the Fsr-regulated gelatinase (gelE), allowing biofilm to grow unchecked by the immune system. Consistent with our pre-clinical findings, analysis of two IE patient cohorts linked naturally occurring Fsr-deficient E. faecalis to prolonged bacteremia. Overall, our findings provide insights into the role of QS in biofilm growth, persistence, and immune evasion in enterococcal IE.

microbiology↗

bioRxiv2022

Regulation and Function of a Polarly Localized Lignin Barrier in the Exodermis

Multicellular organisms control interactions with their environment through the development of specialized barriers in specific cell types. A conserved barrier in plant roots is the endodermal Casparian strip (CS). The CS is made of polymerized lignin and forms a ring-like structure that seals the apoplastic space between the endodermal cells. Most angiosperms also have another root cell type, the exodermis, that is reported to form a barrier. Our understanding of exodermal developmental and molecular regulation, as well as function, is limited as this cell type is absent from the model species Arabidopsis thaliana. Using tomato (Solanum lycopersicum) as a model system we demonstrate that in this species, the exodermis does not form a CS. Instead, it forms a polar lignin cap with an equivalent barrier function to the endodermal CS. We demonstrate that although endodermal regulators are conserved between Arabidopsis and tomato, exodermal differentiation occurs by a distinct regulatory pathway involving the SlSCZ and SlEXO1 transcription factors. Although the exodermis and endodermis both produce barriers that restrict mineral ion uptake, they have unique and overlapping roles in their selectivity. Whether conservation and similarities between the endodermis and exodermis exist in other species remains to be determined. Nonetheless, in tomato, these distinct lignin structures have a convergent function with different genetic regulations.

plant biology↗

bioRxiv2022

A suberized exodermis is required for tomato drought tolerance

Plant roots integrate environmental signals and developmental programs using exquisite spatiotemporal control. This is apparent in the deposition of suberin, an apoplastic diffusion barrier, which regulates the entry and exit of water, solutes and gases, and is environmentally plastic. Suberin is considered a hallmark of endodermal differentiation, but we find that it is absent in the tomato endodermis during normal development. Instead, suberin is present in the exodermis, a cell type that is absent in the model organism Arabidopsis thaliana. Here, we uncover genes driving exodermal suberization and describe its effects on drought responses in tomato, unravelling the similarities and differences with the paradigmatic Arabidopsis endodermis. Cellular resolution imaging, gene expression, and mutant analyses reveal loss of this program from the endodermis, and its co-option in the exodermis. Functional genetic analyses of the tomato MYB92 transcription factor and ASFT enzyme demonstrate the importance of exodermal suberin for a plant water-deficit response. Controlling the degree of exodermal suberization could be a new strategy for breeding climate-resilient plants.

plant biology↗

bioRxiv2020

Innovation, conservation and repurposing of gene function in plant root cell type development

Plant species have evolved myriads of solutions to adapt to dynamic environments, including complex cell type development and regulation. To understand this diversity, we profiled tomato root cell type translatomes and chromatin accessibility. Using xylem differentiation in tomato, relative to Arabidopsis, examples of functional innovation, repurposing and conservation of transcription factors are described. Repurposing and innovation of genes are further observed within an exodermis regulatory network and illustrate its function. Translatome analyses of rice, tomato and Arabidopsis tissues suggest that root meristems are more conserved, and that the functions of constitutively expressed genes are more conserved than those of cell type/tissue-enriched genes. These observations suggest that higher-order properties of cell type and pan-cell type regulation are conserved between plants and animals. One Sentence SummaryPan-species cell type translatome and chromatin accessibility data reveal novelty, conservation and repurposing of gene function.

genomics↗