Restraining Staphylococcus aureus Virulence Factors and Quorum Sensing through Lactic Acid Bacteria Supernatant Extracts

DÍAZ, MYRIAM ANABEL; VEGA-HISSI, ESTEBAN GABRIEL; BLÁZQUEZ, MARÍA AMPARO; ALBERTO, MARÍA ROSA; ARENA, MARIO EDUARDO

Antibiotics

MDPI

Año: 2024 vol. 13

Abstract: The escalating prevalence of antibiotic-resistant bacteria poses a grave threat to humanhealth, necessitating the exploration of novel alternatives to conventional antibiotics. This studyinvestigated the impact of extracts derived from the supernatant of four lactic acid bacteria strains onfactors contributing to the pathogenicity of three Staphylococcus aureus strains. The study evaluatedthe influence of lactic acid bacteria supernatant extracts on the growth, biofilm biomass formation,biofilm metabolic activity, and biofilm integrity of the S. aureus strains. Additionally, the impacton virulence factors (hemolysin and coagulase) was examined. Gas chromatography coupled withmass spectrometry was used to identify the bioactive compounds in the extracts, while moleculardocking analyses explored potential interactions. Predominantly, the extracts contain eight2,5-diketopiperazines, which are cyclic forms of peptides. The extracts demonstrated inhibitory effects on biofilm formation, the ability to disrupt mature biofilms, and reduce the biofilm cell metabolic activity of the S. aureus strains. Furthermore, they exhibited the ability to inhibit α-hemolysin production and reduce coagulase activity. An in silico docking analysis reveals promising interactions between 2,5-diketopiperazines and key proteins (SarA and AgrA) in S. aureus, confirming their antivirulence and antibiofilm activities. These findings suggest that 2,5-diketopiperazines could serve as a promising lead compound in the fight against antibiotic-resistant S. aureus.