Synergy between nanoplastics and benzo[a]pyrene promotes senescence by aggravating ferroptosis and impairing mitochondria integrity in Caenorhabditis elegans.

Micro-nano plastics have been reported as important carriers of polycyclic aromatic hydrocarbons (PAHs) for long-distance migration in the environment. However, the combined toxicity from long-term chronic exposure beyond the vehicle-release mechanism remains elusive. In this study, we investigated the synergistic action of Benzo[a]pyrene (BaP) and Polystyrene nanoparticles (PS) in Caenorhabditis elegans (C. elegans) as a combined exposure model with environmental concentrations. We found that the combined exposure to BaP and PS, as opposed to single exposures at low concentrations, significantly shortened the lifespan of C. elegans, leading to the occurrence of multiple senescence phenotypes. Multi-omics data indicated that the combined exposure to BaP and PS is associated with the disruption of glutathione homeostasis. Consequently, the accumulated reactive oxygen species (ROS) cannot be effectively cleared, which is highly correlated with mitochondrial dysfunction. Moreover, the increase in ROS promoted lipid peroxidation in C. elegans and downregulated Ferritin-1 (Ftn-1), resulting in ferroptosis and ultimately accelerating the aging process of C. elegans. Collectively, our study provides a new perspective to explain the long-term compound toxicity caused by BaP and PS at real-world exposure concentrations.

Role of Type VI secretion system in pathogenic remodeling of host gut microbiota during Aeromonas veronii infection.

Intestinal microbial disturbance is a direct cause of host disease. The bacterial Type VI secretion system (T6SS) often plays a crucial role in the fitness of pathogenic bacteria by delivering toxic effectors into target cells. However, its impact on the gut microbiota and host pathogenesis is poorly understood. To address this question, we characterized a new T6SS in the pathogenic Aeromonas veronii C4. First, we validated the secretion function of the core machinery of A. veronii C4 T6SS. Second, we found that the pathogenesis and colonization of A. veronii C4 is largely dependent on its T6SS. The effector secretion activity of A. veronii C4 T6SS not only provides an advantage in competition among bacteria in vitro, but also contributes to occupation of an ecological niche in the nutritionally deficient and anaerobic environment of the host intestine. Metagenomic analysis showed that the T6SS directly inhibits or eliminates symbiotic strains from the intestine, resulting in dysregulated gut microbiome homeostasis. In addition, we identified three unknown effectors, Tse1, Tse2, and Tse3, in the T6SS, which contribute to T6SS-mediated bacterial competition and pathogenesis by impairing targeted cell integrity. Our findings highlight that T6SS can remodel the host gut microbiota by intricate interplay between T6SS-mediated bacterial competition and altered host immune responses, which synergistically promote pathogenesis of A. veronii C4. Therefore, this newly characterized T6SS could represent a general interaction mechanism between the host and pathogen, and may offer a potential therapeutic target for controlling bacterial pathogens.