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In vivo antimicrobial therapeutic efficacy and immune homeostasis analysis of S. aureus peritonitis

ABSTRACT: Type-I photosensitization addresses the dilemma of intracellular bacterial hypoxia-induced photodynamic therapeutic (PDT) inefficacy, yet precise targeting and eradicating sequestered pathogens remains a formidable challenge. Herein, we engineer an albumin-based photodynamic conversion nanomedicine integrating target-specific recognition with controlled antibacterial functions to precisely eliminate intracellular pathogens and restore infected cell activity. Mechanistic studies reveal a vertically-crossed conformation that promotes intramolecular electron transfer and charge separation, redirecting photosensitizer (PS) reactivity toward type-I reactive oxygen species (ROS) generation. Electron-rich albumin further enhances cationic PS+• recycling, photostability and O2-• generation, while minimizing off-target organelle effects. We demonstrate application in S. aureus-infected sepsis showing high type-I ROS levels for antibacterial function from the nanomedicine to restore redox and immune homeostasis without noticeable toxicity. This work pioneers a strategy to convert ROS generation from type-II to type-I pathways for hypoxia-tolerant bacterial elimination, merging mechanistic precision with translational potential for clinical sepsis management.

ORGANISM(S): Mus musculus

PROVIDER: GSE315421 | GEO | 2026/05/01

REPOSITORIES: GEO

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Project description:Introduction: Sepsis is a complex immunological response to infection characterized by early hyperinflammation followed by severe and protracted immunosuppression, suggesting that a multi-marker approach has the greatest clinical utility for early detection, within a clinical environment focused on SIRS differentiation. Pre-clinical research using an equine sepsis model identified a panel of gene expression biomarkers that define the early aberrant immune activation. Thus, the primary objective was to apply these gene expression biomarkers to distinguish patients with sepsis from those who had undergone major open surgery and had clinical outcomes consistent with systemic inflammation due to physical trauma and wound healing. Methods: This was a multi-centre, prospective clinical trial conducted across 4 tertiary critical care settings in Australia. Sepsis patients were recruited if they met the 1992 Consensus Statement criteria and had clinical evidence of systemic infection based on microbiology diagnoses (n=27). Participants in the post-surgical (PS) group were recruited pre-operatively and blood samples collected within 24 hours following surgery (n=38). Healthy controls (HC) included hospital staff with no known concurrent illnesses (n=20). Each participant had minimally 5ml of PAXgene blood collected for leucocyte RNA isolation and gene expression analyses. Affymetrix array and multiplex tandem (MT)-PCR studies were conducted to evaluate transcriptional profiles in circulating white blood cells applying a set of 42 molecular markers that had been identified a priori. A LogitBoost algorithm was used to create a machine learning diagnostic rule to predict sepsis outcomes. Results: Based on preliminary microarray analyses comparing HC and sepsis groups. A panel of 42-gene expression markers were identified that represented key innate and adaptive immune function, cell cycling, WBC differentiation, extracellular remodelling and immune modulation pathways. Comparisons against GEO data confirmed the definitive separation of the sepsis cohort. Quantitative PCR results suggest the capacity for this test to differentiate severe systemic inflammation from HC is 92%. AUC ROC curve findings demonstrated sepsis prediction within a mixed inflammatory population, was between 86 - 92%. Conclusions: This novel molecular biomarker test has a clinically relevant sensitivity and specificity profile, and has the capacity for early detection of sepsis via the monitoring of critical care patients. GEO Note: Data made available represents the preliminary microarray investigation performed on Human U133 Plus 2.0 GeneChips (Affymetrix), assaying 41 patient samples (Sepsis n=10, Post-Surgical n=11, Control n=20). This was a multi-centre, prospective clinical trial conducted across 4 tertiary critical care settings in Australia. Sepsis patients were recruited if they met the 1992 Consensus Statement criteria and had clinical evidence of systemic infection based on microbiology diagnoses (n=27). Participants in the post-surgical (PS) group were recruited pre-operatively and blood samples collected within 24 hours following surgery (n=38). Healthy controls (HC) included hospital staff with no known concurrent illnesses (n=20). Each participant had minimally 5ml of PAXgene blood collected for leucocyte RNA isolation and gene expression analyses. The GEO data represents the preliminary microarray investigation performed on Human U133 Plus 2.0 GeneChips (Affymetrix), assaying 41 patient samples (Sepsis n=10, Post-Surgical n=11, Control n=20).

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In vivo antimicrobial therapeutic efficacy and immune homeostasis analysis of S. aureus peritonitis

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