Rapamycin and caspofungin show synergistic antifungal effects in caspofungin-susceptible and caspofungin-resistant Candida strains in vitro.

OBJECTIVES: Caspofungin is an echinocandin antifungal agent that inhibits synthesis of glucan required for the fungal cell wall. Resistance is mediated by mutation of Fks1 glucan synthase, among which S645P is the most common resistance-associated polymorphism. Rapamycin is a macrolide that inhibits the mechanistic target of rapamycin (mTOR) protein kinase activity. This study investigated the interaction between rapamycin and caspofungin in inhibiting the growth of WT Candida albicans and Fks1 S645P mutant clinical isolate, and WT Candida lusitaniae and genetically engineered isogenic strain with Fks1 S645P mutation at equivalent position. METHODS: Interactions between caspofungin and rapamycin were evaluated using the microdilution chequerboard method in liquid medium. The results were analysed using the Loewe additivity model (FIC index, FICI) and the Bliss independence model (response surface, RS, analysis). RESULTS: Synergy between rapamycin and caspofungin was shown for C. albicans and C. lusitaniae strains by RS analysis of the chequerboard tests. Synergy was observed in strains susceptible and resistant to caspofungin. Weak subinhibitory concentrations of rapamycin were sufficient to restore caspofungin susceptibility. CONCLUSIONS: We report here, for the first time, synergy between caspofungin and rapamycin in Candida species. Synergy was shown for strains susceptible and resistant to caspofungin. This study highlights the possible implication of the TOR pathway in sensing antifungal-mediated cell wall stress and in modulating the cellular response to echinocandins in Candida yeasts.

The gut-lung axis in the CFTR modulator era.

The advent of CFTR modulators represents a turning point in the history of cystic fibrosis (CF) management, changing profoundly the disease's clinical course by improving mucosal hydration. Assessing changes in airway and digestive tract microbiomes is of great interest to better understand the mechanisms and to predict disease evolution. Bacterial and fungal dysbiosis have been well documented in patients with CF; yet the impact of CFTR modulators on microbial communities has only been partially deciphered to date. In this review, we aim to summarize the current state of knowledge regarding the impact of CFTR modulators on both pulmonary and digestive microbiomes. Our analysis also covers the inter-organ connections between lung and gut communities, in order to highlight the gut-lung axis involvement in CF pathophysiology and its evolution in the era of novel modulators therapies.

Effect of a Black Soldier Fly Ingredient on the Growth Performance and Disease Resistance of Juvenile Pacific White Shrimp (Litopenaeus vannamei).

This study was performed as part of developing a functional feed ingredient for juvenile Pacific white shrimp (Litopenaeus vannamei). Here we assess the effects of dietary inclusion of a Black Soldier Fly Ingredient (BSFI) from defatted black soldier fly (Hermetia illucens) larvae meal on growth performance, tolerance to salinity stress, and disease resistance when challenged with Vibrio parahaemolyticus or a strain of white spot syndrome virus (WSSV). A control diet was used for comparison with three test diets including 4.5, 7.5, and 10.5% of BSFI (BSFI4.5, BSFI7.5, and BSFI10.5). After 28 days, all diets with BSFI had improved weight gain, feed conversion ratio (FCR) and specific growth rate (SGR) compared to control. Indeed, SGR was significantly improved from inclusion of 4.5% in the diet, whilst FCR was significantly improved at 7.5% (p < 0.05). During the growth trial, survival was not affected by diet. Shrimp health performance was not significantly affected by the diets across the disease and salinity challenges. Overall, the results indicate that the inclusion of BSFI from H. illucens improves the performance of juvenile L. vannamei.