Targeting Candida albicans O-acetyl-L-homoserine sulfhydrylase (Met15p) in antifungal treatment.

Fungal infections are a serious threat to public health as they are becoming increasingly frequent. A major problem stems also from a rising fungal resistance to currently available antifungal therapies, therefore novel molecular targets are highly desirable. Exploration of enzymes participating in the biosynthesis pathways of essential amino acids such as L-methionine (L-Met) may provide new insights into pharmaceutical development.

N-3 Polyunsaturated Fatty Acids as a Nutritional Support of the Reproductive and Immune System of Cattle-A Review.

This paper focuses on the role of n-3 fatty acids as a nutrient crucial to the proper functioning of reproductive and immune systems in cattle. Emphasis was placed on the connection between maternal and offspring immunity. The summarized results confirm the importance and beneficial effect of n-3 family fatty acids on ruminant organisms.

Dual-Activity Fluoroquinolone-Transportan 10 Conjugates Offer Alternative Leukemia Therapy during Hematopoietic Cell Transplantation.

Hematopoietic cell transplantation (HCT) is often considered a last resort leukemia treatment, fraught with limited success due to microbial infections, a leading cause of mortality in leukemia patients. To address this critical issue, we explored a novel approach by synthesizing antileukemic agents containing antibacterial substances. This innovative strategy involves conjugating fluoroquinolone antibiotics, such as ciprofloxacin (CIP) or levofloxacin (LVX), with the cell-penetrating peptide transportan 10 (TP10).

Fatty acids as molecular carriers in cleavable antifungal conjugates.

Conjugates composed of C fatty acid (FA) residues as a molecular carrier and 5-fluorocytosine (5-FC) as an active agent, released upon the action of intracellular esterases on the ester bond between FA and "trimethyl lock" intramolecular linker, demonstrate good in vitro activity against human pathogenic yeasts of Candida spp. The minimal inhibitory concentrations (MIC) values for the most active conjugates containing caprylic (C), capric (C), lauric (C), or myristic (C) acid residues were in the 2-64 μg mL range, except for these against the least susceptible Candida krusei. The least active conjugates containing C, C or C FA were slowly hydrolyzed by esterase and probably poorly taken up by Candida cells, as found for their analogs containing a fluorescent label, Nap-NH instead of 5-FC.

Antifungal Effect of Penicillamine Due to the Selective Targeting of L-Homoserine -Acetyltransferase.

Due to the apparent similarity of fungal and mammalian metabolic pathways, the number of established antifungal targets is low, and the identification of novel ones is highly desirable. The results of our studies, presented in this work, indicate that the fungal biosynthetic pathway of L-methionine, an amino acid essential for humans, seems to be an attractive perspective. The gene from encoding L-homoserine -acetyltransferase (Met2p), an enzyme catalyzing the first step in that pathway, was cloned and expressed as the native or the oligo-His-tagged fusion protein in .