Biology subjects

Ortega, E.

Publications and source records attributed to Ortega, E..

4 recordsLinked to original sources

bioRxiv2026

Eggerthella lenta evades bacteriophage through reversible megabase-scale inversions of capsular polysaccharide gene clusters

Bacteriophages are a promising tool for microbiome editing, yet their development has been constrained by limited insights into bacteriophage-host interactions within their shared mammalian body habitat. We isolated a lytic phage {Phi}KL11 that efficiently targets a disease-associated member of the human gut microbiota, Eggerthella lenta, during in vitro growth. However, {Phi}KL11 selects for a pre-existing and reversible bacteriophage-resistant sub-population in mice. Long-read sequencing revealed a massive genomic inversion event, representing >50% of the E. lenta genome, enriched in response to bacteriophage infection. Transcriptomics linked this inversion to the altered expression of three capsular polysaccharide synthesis (CPS) gene clusters and transmission electron microscopy confirmed differential capsule production. Finally, we show that {Phi}KL11 has a broad host range attributable to CPS and other strain-variable genes. These findings suggest a previously unrecognized strategy for phage evasion in the gut, involving megabase-scale genomic inversions and reversible capsule variation driving phage resistance.

microbiology↗

bioRxiv2026

Female-enriched Eggerthella lenta drives neuroinflammation and IFN-γ via host receptor TLR2

Women are at increased risk of autoimmune diseases, including multiple sclerosis (MS); however, the degree to which sex differences in the gut microbiota impact autoimmunity remains largely unexplored. Our 27-cohort meta-analysis revealed 60 sex-associated gut bacterial species. Leveraging an independent clinical cohort, we demonstrate that female-enriched species significantly associate with MS status and clinical disability (EDSS). Top female-enriched species Eggerthella lenta drove disease in the experimental autoimmune encephalomyelitis (EAE) MS model, consistent with brain and gut lamina propria T cell infiltration and MS-associated T helper (Th) signatures. E. lenta induced intestinal Th1 and Th17 in healthy mice, independent of bacterial viability. Mechanistically, we demonstrate that TLR2 directly drives E. lenta-induced IFN-{gamma} production in Th cells and is necessary for exacerbation of EAE. Together, we identify a causal host-microbe axis contributing to sex differences in autoimmunity and provide a framework for evaluating sex as a biological variable in human microbiome research. HIGHLIGHTSO_LI27-cohort meta-analysis identifies a robust sex-signature in human gut microbiota. C_LIO_LIFemale-enriched species are associated with MS risk and severity. C_LIO_LIFemale-enriched Eggerthella lenta exacerbates the EAE model. C_LIO_LIE. lenta impacts neuroinflammation via toll-like receptor 2. C_LI

microbiology↗

bioRxiv2024

Prefrontal 5α-reductase 2 mediates male-specific acute stress response

A key response to acute stress is the increased brain synthesis of the neurosteroid allopregnanolone (AP). While the rate-limiting step of this reaction is catalyzed by 5-reductase (5R), the role of its two primary isoenzymes, 5R1 and 5R2, in stress reactivity remains unclear. Here, we found that acute stress led to increased levels of 5R2, but not 5R1, in the medial prefrontal cortex (mPFC) of male, but not female, rats. Downregulation of 5R2 in the mPFC significantly reduced stress response in males, and similar sexual dimorphic effects were observed in a novel line of 5R2 knockout rats. Notably, 5R1 regulated baseline AP synthesis, while 5R2 enabled AP production under stress. Acute AP administration restored stress response in 5R2 knockdown rats. Single-nucleus transcriptomics showed that 5R2 enabled stress-induced protein translation in neurons and glia. These results highlight the crucial role of 5R2 in mediating sex-specific differences in acute stress reactivity.

neuroscience↗

bioRxiv2021

Inside-out Signalling From Aminopeptidase N (CD13) To Complement Receptor 3 (CR3, CD11b/CD18)

Upon ligand engagement, certain receptors can activate an integrin through a mechanism called inside-out signalling. This phenomenon prepares the cell for the next steps of the process it will perform. CR3 (Complement receptor 3), the most abundant {beta}2 integrin in monocytes and macrophages, and CD13 (aminopeptidase N) are two immune receptors with overlapping activities: adhesion, phagocytosis of opsonized particles, and respiratory burst induction. They can be found together in functional signalling microdomains, or lipid rafts, on the surface of human leukocytes. Thus, given their common functions, shared physical location and the fact that some phagocytic and adhesion receptors activate a selection of integrins, we hypothesized that CD13 could activate CR3 through an inside-out signalling mechanism. To test this hypothesis, we first ascertained the activation of CR3 after CD13 crosslinking in human monocyte-derived macrophages. We used an integrated analysis of bioinformatics and experimental data to suggest two possible signalling cascades that could explain the phenomenon. Finally, we show that the non-receptor tyrosine kinase Syk is a key attenuator of this pathway. Our results demonstrated that, even in the absence of canonical signalling motifs, and despite having a noticeably short cytoplasmic tail (7-10 amino acids), CD13 was capable of triggering an inside-out signalling cascade, adding a new function to those already known for this moonlighting protein. One Sentence SummaryStimulation of CD13 activated the integrin CR3 via an inside-out signalling pathway, a mechanistic model is proposed.

immunology↗