The rise of antibiotic resistance, particularly among pathogens such as methicillin-resistant Staphylococcus aureus, necessitates innovative antibacterial strategies. Here we introduce FibriLysins, a class of engineered enzymes combining staphylokinase and endolysin, which dismantle fibrin-encapsulated multicellular staphylococcal communities, including biofilms and staphylococcal abscess communities (SACs). We characterized diverse staphylokinases, developing a library of 27 FibriLysins, with a 78% positive hit rate. The lead variant, FL-028, has significant antibacterial activity against prevalent clinical S. aureus isolates. In vitro, FL-028 reduced bacterial counts in SACs by 3.4 log and in biofilms by 2.3 log. In vivo, FL-028 exhibits superior efficacy in a mouse model of bone fracture-related infection, outperforming vancomycin by 1 log and eliminating SAC presence in tissues. FL-028 shows no adverse effects on bone healing, as confirmed by histological examination, mechanical testing and micro-computed tomography analyses. These preclinical findings highlight the potential of FibriLysins as a robust and safe therapeutic approach against difficult-to-treat staphylococcal infections. Engineered FibriLysins dismantle fibrin-encapsulated Staphylococcus aureus communities and outperform vancomycin in a preclinical model of fracture-related infection.
Antibody-dependent enhancement of dengue virus infection is widely thought to explain severe dengue. However, there are multiple other interdependent pathobiological steps that could contribute to potentially life-threatening disease.
Fusobacterium nucleatum-derived 2-hydroxybutyrate promotes toxin expression by enterotoxigenic Bacteroides fragilis in the mouse gut, which drives persistent enteric neuron loss and intestinal dysmotility long after bacterial infection is cleared.
The coral microbiome is believed to play a crucial role in sustaining corals and enabling adaptation to perturbations. A ubiquitous group of coral-associated bacteria, known as Endozoicomonas, are hypothesized to provide essential metabolites to corals, although detailed dynamics of the interactions between host and microbe are poorly understood. Here multi-omics and laboratory validation experiments reveal that Endozoicomonas encodes genes for the metabolism of coral-derived testosterone and converts ubiquitous cholesterol into testosterone and progesterone, both important steroids that accumulate within the coral holobiont during thermal stress. Field sampling along a natural temperature gradient showed general suppression of coral steroid hormones under thermal stress and during white syndrome manifestation. Provision of testosterone or progesterone to corals during laboratory thermal stress induced transcriptional reprogramming of the coral innate immune response, suggesting microbial involvement in host immune modulation. These findings highlight a previously unrecognized potential mechanism of microbial contribution to coral resilience. Multi-omics and laboratory experiments reveal that a coral-associated bacterium can produce testosterone and progesterone; these two hormones alter the coral host’s innate immune responses during thermal stress.
Chronic airway infection and inflammation form a destructive partnership in cystic fibrosis. Recent evidence shows that Pseudomonas aeruginosa persistent infections can redirect immunity towards tissue injury.
