Investigation of the biocontrol mechanism of a novel Pseudomonas species against phytopathogenic Fusarium graminearum revealed by multi-omics integration analysis.

Phytopathogenic Fusarium graminearum poses significant threats to crop health and soil quality. Although our laboratory-cultivated Pseudomonas sp. P13 exhibited potential biocontrol capacities, its effectiveness against F. graminearum and underlying antifungal mechanisms are still unclear. In light of this, our study investigated a significant inhibitory effect of P13 on F. graminearum T1, both in vitro and in a soil environment. Conducting genomic, metabolomic, and transcriptomic analyses of P13, we sought to identify evidence supporting its antagonistic effects on T1. The results revealed the potential of P13, a novel Pseudomonas species, to produce active antifungal components, including phenazine-1-carboxylate (PCA), hydrogen cyanide (HCN), and siderophores [pyoverdine (Pvd) and histicorrugatin (Hcs)], as well as the dynamic adaptive changes in the metabolic pathways of P13 related to these active ingredients. During the logarithmic growth stage, T1-exposed P13 strategically upregulated PCA and HCN biosynthesis, along with transient inhibition of the tricarboxylic acid (TCA) cycle. However, with growth stabilization, upregulation of PCA and HCN synthesis ceased, whereas the TCA cycle was enhanced, increasing siderophores secretion (Pvd and Hcs), suggesting that this mechanism might have caused continuous inhibition of T1. These findings improved our comprehension of the biocontrol mechanisms of P13 and provided the foundation for potential application of Pseudomonas strains in the biocontrol of phytopathogenic F. graminearum. IMPORTANCE: Pseudomonas spp. produces various antifungal substances, making it an effective natural biocontrol agent against pathogenic fungi. However, the inhibitory effects and the associated antagonistic mechanisms of Pseudomonas spp. against Fusarium spp. are unclear. Multi-omics integration analyses of the in vitro antifungal effects of novel Pseudomonas species, P13, against F. graminearum T1 revealed the ability of P13 to produce antifungal components (PCA, HCN, Pvd, and Hcs), strategically upregulate PCA and HCN biosynthesis during logarithmic growth phase, and enhance the TCA cycle during stationary growth phase. These findings improved our understanding of the biocontrol mechanisms of P13 and its potential application against pathogenic fungi.

Hyperactive lateral habenula mediates the comorbidity between rheumatoid arthritis and depression-like behaviors.

Rheumatoid arthritis (RA) patients have a high prevalence for depression. On the other hand, comorbid with depression is associated with worse prognosis for RA. However, little is known about the underlying mechanisms for the comorbidity between RA and depression. It remains to be elucidated which brain region is critically involved in the development of depression in RA, and whether alterations in the brain may affect pathological development of RA symptoms. Here, by combining clinical and animal model studies, we show that in RA patients, the level of depression is significantly correlated with the severity of RA disease activity and affects patients' quality of life. The collagen antibody-induced arthritis (CAIA) mouse model of RA also develops depression-like behaviors, accompanied by hyperactivity and alterations in gene expression reflecting cerebrovascular disruption in the lateral habenula (LHb), a brain region critical for processing negative valence. Importantly, inhibition of the LHb not only alleviates depression-like behaviors, but also results in rapid remission of RA symptoms and amelioration of RA-related pathological changes. Together, our study highlights a critical but previously overlooked contribution of hyperactive LHb to the comorbidity between RA and depression, suggesting that targeting LHb in conjunction with RA treatments may be a promising strategy for RA patients comorbid with depression.

A life-and-death struggle: interaction of insects with entomopathogenic fungi across various infection stages.

Insects constitute approximately 75% of the world's recognized fauna, with the majority of species considered as pests. Entomopathogenic fungi (EPF) are parasitic microorganisms capable of efficiently infecting insects, rendering them potent biopesticides. In response to infections, insects have evolved diverse defense mechanisms, prompting EPF to develop a variety of strategies to overcome or circumvent host defenses. While the interaction mechanisms between EPF and insects is well established, recent findings underscore that their interplay is more intricate than previously thought, especially evident across different stages of EPF infection. This review primarily focuses on the interplay between EPF and the insect defense strategies, centered around three infection stages: (1) Early infection stage: involving the pre-contact detection and avoidance behavior of EPF in insects, along with the induction of behavioral responses upon contact with the host cuticle; (2) Penetration and intra-hemolymph growth stage: involving the initiation of intricate cellular and humoral immune functions in insects, while symbiotic microbes can further contribute to host resistance; (3) Host insect's death stage: involving the ultimate confrontation between pathogens and insects. Infected insects strive to separate themselves from the healthy population, while pathogens rely on the infected insects to spread to new hosts. Also, we discuss a novel pest management strategy underlying the cooperation between EPF infection and disturbing the insect immune system. By enhancing our understanding of the intricate interplay between EPF and the insect, this review provides novel perspectives for EPF-mediated pest management and developing effective fungal insecticides.