Background: The emergence of antibiotic-resistant bacteria, including Staphylococcus epidermidis, underscores the need for novel antimicrobial agents. Celastrol, a natural compound derived from the plants of the Celastraceae family, has demonstrated promising antibacterial and antibiofilm properties against various pathogens. Objectives: This study aims to evaluate the antibacterial effects, mechanism of action, and antibiofilm activity of celastrol against S. epidermidis, an emerging opportunistic pathogen. Methods: To investigate the mechanism of action of celastrol, its antibacterial activity was evaluated by determining the time–kill curves, assessing macromolecular synthesis, and analysing its impact on the stability and functionality of the bacterial cell membrane. Additionally, its effect on biofilm formation and disruption was examined. Results: Celastrol exhibited significant antibacterial activity with a minimal inhibitory concentration (MIC) of 0.31 μg/mL and minimal bactericidal concentration (MBC) of 15 μg/mL, which is superior to conventional antibiotics used as control. Time–kill assays revealed a concentration-dependent bactericidal effect, with a shift from bacteriostatic activity at lower concentrations to bactericidal and lytic effect at higher concentrations. Celastrol inhibited cell wall biosynthesis by blocking the incorporation of N-acetylglucosamine (NAG) into peptidoglycan. In contrast, the cytoplasmic membrane was only affected at higher concentrations of the compound or after prolonged exposure times. Additionally, celastrol was able to disrupt biofilm formation at concentrations of 0.9 μg/mL and to eradicate pre-formed biofilms at 7.5 μg/mL in S. epidermidis. Conclusions: Celastrol exhibits significant antibacterial and antibiofilm activities against S. epidermidis, with a primary action on cell wall synthesis. Its efficacy in disrupting the formation of biofilms and pre-formed biofilms suggests its potential as a therapeutic agent for infections caused by biofilm-forming S. epidermidis resistant to conventional treatments.

Introduction. Infections caused by pathogenic fungi present a persistent public health challenge. Marine invertebrates, such as sea cucumbers (holothurians), are recognized for their high protein content and various medicinal properties. They also serve as reservoirs of bioactive compounds. In the territorial waters of México, six sea cucumber species, including Astichopus multifidus, Isostichopus badionotus, and Holothuria floridana, are found along the Yucatán Peninsula. However, overexploitation threatens these species, potentially diminishing valuable sources of antimicrobial agents. Objectives. This study aims to evaluate the antifungal activity of organic extracts from A. multifidus and H. floridana against various fungal strains, using minimum inhibitory concentration (MIC) and minimum fungicidal concentration (MFC) assays. Materials and Methods. Organic extracts from A. multifidus and H. floridana were obtained and tested for antifungal activity using a microdilution method. The MIC and MFC values were determined against a panel of fungal strains, including Trichophyton rubrum, Aspergillus niger, and Cryptococcus neoformans. Extracts from Isostichopus badionotus were also evaluated. Results and Discussion. Approximately 50% of the extracts exhibited antifungal activity. Butanolic body extracts from A. multifidus and H. floridana displayed the lowest MIC values (15.6 µg/mL) against T. rubrum and A. niger, respectively. Additionally, these extracts demonstrated antifungal activity (31.2 µg/mL) against C. neoformans. In contrast, extracts from I. badionotus showed no activity. These results suggest that A. multifidus and H. floridana contain bioactive compounds with antifungal potential. Conclusions. The antifungal properties of A. multifidus and H. floridana highlight their potential as sources of novel antifungal agents. Their sustainable use could contribute to the development of new antifungals