Daily Sepsis Research Analysis

Antimicrobial peptides (AMPs) are promising alternatives to overcome antimicrobial resistance (AMR). However, precise construction of an AMP targeting bacterial cell membranes derived from natural peptides remains a great challenges. Although the artificial intelligence (AI) algorithm-assisted screening method has achieved unprecedented successes, it's difficult to predict the targets of AMPs obtained from this method. To address this, an AMP (P 3-3R-8I) based on several natural peptides derived from insect cuticle was constructed precisely via amino acid mutation. The mutated amino acids Arginine (R) and Isoleucine (I) are expected to target the bacterial cell membranes. Surprisingly, P 3-3R-8I exhibits super antibacterial capability against two representative bacteria: methicillin-resistant Staphylococcus aureus (MRSA) and Escherichia coli (E. coli), which could be attributed to the ability to quickly penetrate bacterial cell membranes and then to bind to bacterial DNA of P 3-3R-8I, resulting in the suppression of DNA replication. In rats' model, the MRSA-infected wound could be alleviated by P 3-3R-8I obviously, as well as lung and spleen infections in MRSA-induced systemic sepsis. Our findings provide a prospect for the precise construction of AMPs targeting bacterial cell membranes as well as a means of overcoming AMR, offering a strategy for drug-resistant bacteria-induced tissue repair.

BACKGROUND: One third of patients with Escherichia coli bacteraemia develop a dysregulated inflammatory response (sepsis/septic shock). Our objective was to investigate whether specific microbiological determinants of E. coli are associated to presentation with sepsis/shock. METHODS: A matched case-control study was performed; 101 case-patients with E. coli bacteraemia presenting with sepsis (SEPSIS-3 criteria) and 101 control-patients with E. coli bacteraemia without sepsis were matched by service, sex, age, Charlson index, acquisition and source of the bacteraemia and empirical treatment. Whole genome sequencing of E. coli isolates was performed (Illumina MiSeq Inc.). Sequence type, serotype, fimH type, virulence factors, antibiotic resistance genes, plasmid replicons pathogenicity islands and prophages were determined. A multivariate model was built for presentation with sepsis/septic shock using conditional logistic regression. The predictive capacity on the observed data was measured with the area under the ROC curve (AUROC) with 95% confidence intervals (CI). RESULTS: Here we show that in the multivariate model (adjusted OR; 95% CI), the ST69 clone (7.53; 1.06-35.05) and pic gene (4.38; 1.53-12.54) are associated to presentation with sepsis/shock, while the genes papC (0.30; 0.12-0.74) and fdeC (0.18; 0.03-1.32) show a protective effect. The AUROC of this model is 0.81 (95% CI 0.74-0.87). CONCLUSIONS: We identify E. coli bacterial factors associated with severe clinical presentation in patients with bacteraemia. Further studies would be needed to consider these factors as potential preventive or therapeutic targets. Escherichia coli is the most common cause of invasive infections, including bacteraemia that often progresses to severe conditions like sepsis or septic shock. While many host factors determine the severity of illness, this study looked at the bacterial factors that may contribute to sepsis severity. We directly compared E. coli-infected patients with similar traits but either with or without sepsis to control for patient factors Our analysis revealed that the ST69 clone and the presence of the pic gene were significantly associated with an increased risk of sepsis/septic shock, whereas the adhesion genes papC and fdeC were associated with a lower risk. These key findings underscore a role for specific E. coli genetic factors in determining clinical severity, thereby providing potential bacterial targets for the development of improved diagnostics and novel preventive or therapeutic interventions.

BACKGROUND: Sepsis and septic shock are life-threatening conditions with high mortality, presenting challenges in predicting disease severity and outcomes. Cell-free mitochondrial DNA (mtDNA) has emerged as a potential mediator in sepsis pathogenesis, acting as a damage-associated molecular pattern (DAMP) that exacerbates inflammation. The present study aimed to assess cell-free mtDNA levels as predictors of mortality and disease severity, and to determine their correlation with established clinical markers. METHODS: A prospective study enrolled 150 participants, including healthy controls (n = 50) and patients (n = 100, of which 50 had sepsis and 50 had septic shock). Plasma cell-free mtDNA levels were quantified using RT-qPCR, and Receiver operating characteristic (ROC) curves were used to evaluate the predictive ability of cell-free mtDNA for 28-day mortality. The cell-free mtDNA correlated with clinical markers, including C-reactive protein (CRP), Sequential Organ Failure Assessment (SOFA), Acute Physiology and Chronic Health Evaluation (APACHE II), Procalcitonin (PCT), neutrophil-to-lymphocyte ratio (NLR), and lactate. RESULTS: Cell-free mtDNA levels were significantly elevated in sepsis and septic shock patients compared to controls, and higher in septic shock compared to sepsis patients. Non-survivors exhibited significantly higher cell-free mtDNA levels than survivors across both sepsis and septic shock subgroups. Cell-free mtDNA demonstrated a superior predictive value for 28-day mortality, area under the curve (AUC = 0.865) compared to clinical markers (CRP, SOFA, PCT, NLR, and Lactate). Furthermore, cell-free mtDNA levels showed a positive correlation with CRP, followed by SOFA, NLR, and PCT. CONCLUSION: Elevated circulating cell-free mtDNA levels were associated with severity and mortality in sepsis and septic shock, and may act as a valuable molecular tool for predicting disease outcomes. The study's findings warrant further investigation into the potential of cell-free mtDNA as a future component of clinical management strategies in sepsis.