Mizrahi, N. | bioRxiv Science

bioRxiv2025

Cocaine- and amphetamine-regulated transcript in perciforms II. Responsiveness to energetic shortage

Cocaine and amphetamine-regulated transcript (Cart) is a neuropeptide with prominent roles in appetite regulation and maintenance of energy homeostasis. Although Cart has been widely studied in vertebrates, its multigenic nature in fish elicits questions regarding the various functions affected by specific cart peptides. This is further emphasized when considering the high variation of aquatic ecosystems fish occupy. Nile tilapia (Oreochromis niloticus) and gilthead seabream (Sparus aurata) are important aquaculture species with different natural habitats, food preferences and feeding behaviors. Herein, we utilize these two species to evaluate whether food-related cart functions are species-specific. To this end, we studied how short-term (SD) or long-term (LD) food deprivation affects the central expression of the multiple cart genes of both species. Quantitative PCR analysis of cart expression demonstrated that SD resulted in decreased midbrain expression of three tilapia carts and three seabream carts while LD decreased the midbrain expression of two tilapia carts and two seabream carts. In addition, SD increased the expression of tilapia oncart1c in the anterior brain and oncart1c and oncart1b in the posterior brain while reducing the expression of seabream sacart1c. Our analyses showed that there are cart genes in each species (cart1a and cart1b for tilapia, and cart1b for seabream) that responded to both SD and LD by reduced expression in the midbrain. In addition, both conditions reduced the expression of seabream sacart1c in the posterior brain. Taken together, our current findings suggest that the major appetite regulation in each species is mediated by species-specific carts.

physiology↗

bioRxiv2023

Candida auris evades innate immunity by using metabolic strategies to escape and kill macrophages while avoiding antimicrobial inflammation

Candida auris causes life-threatening, drug-resistant infections. In addition to drug resistance, therapeutic innovation is hindered by our limited knowledge of the mechanisms used by C. auris to evade immunity and establish infection. Here we show that C. auris escapes phagocytic containment and kills macrophages, and demonstrate that the mechanisms rely on metabolic regulation. We found that C. auris-infected macrophages undergo immunometabolic reprogramming and increase glycolysis but this does not lead to the expected antimicrobial responses, as macrophages fail to activate IL-1{beta} cytokine and curb C. auris growth. Further analysis showed that C. auris relies on its own metabolic capacity to egress from macrophages, cause macrophage metabolic stress and cell death, and establish infection in vivo. We identified a transcriptional regulator of C. auris metabolism and macrophage evasion, and further show that, contrary to several other pathogens, C. auris-induced macrophage metabolic dysfunction and death fail to activate the NLRP3 inflammasome. Consequently, inflammasome-dependent antimicrobial responses remain inhibited throughout infection. Our findings establish a pivotal role for metabolic regulation in enabling C. auris to eliminate macrophages while remaining immunologically silent to ensure its own survival.

microbiology↗