Díaz Myriam Anabel, Vega-Hissi Esteban Gabriel, Blázquez María Amparo, Alberto María Rosa, Arena Mario Eduardo
Instituto Superior de Investigaciones Biológicas (INSIBIO, CONICET-UNT), Chacabuco 461, San Miguel de Tucumán CP 4000, Argentina.
Instituto Multidisciplinario de Investigaciones Biológicas (IMIBIO-SL), Facultad de Química, Bioquímica y Farmacia, Universidad Nacional de San Luis, Ejército de Los Andes 950, San Luis CP 5700, Argentina.
Antibiotics (Basel). 2024 Mar 25;13(4):297. doi: 10.3390/antibiotics13040297.
The escalating prevalence of antibiotic-resistant bacteria poses a grave threat to human health, necessitating the exploration of novel alternatives to conventional antibiotics. This study investigated the impact of extracts derived from the supernatant of four lactic acid bacteria strains on factors contributing to the pathogenicity of three strains. The study evaluated the influence of lactic acid bacteria supernatant extracts on the growth, biofilm biomass formation, biofilm metabolic activity, and biofilm integrity of the strains. Additionally, the impact on virulence factors (hemolysin and coagulase) was examined. Gas chromatography coupled with mass spectrometry was used to identify the bioactive compounds in the extracts, while molecular docking analyses explored potential interactions. Predominantly, the extracts contain eight 2,5-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 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 , 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 .
抗生素耐药细菌的日益流行对人类健康构成了严重威胁，因此有必要探索传统抗生素的新型替代品。本研究调查了四种乳酸菌菌株上清液提取物对三种菌株致病性相关因素的影响。该研究评估了乳酸菌上清液提取物对这些菌株的生长、生物膜生物量形成、生物膜代谢活性和生物膜完整性的影响。此外，还检测了对毒力因子（溶血素和凝固酶）的影响。采用气相色谱-质谱联用技术鉴定提取物中的生物活性化合物，同时通过分子对接分析探索潜在的相互作用。提取物主要含有八种2,5-二酮哌嗪，它们是肽的环状形式。提取物对生物膜形成具有抑制作用，能够破坏成熟生物膜，并降低这些菌株的生物膜细胞代谢活性。此外，它们还表现出抑制α-溶血素产生和降低凝固酶活性的能力。计算机对接分析揭示了2,5-二酮哌嗪与这些菌株中关键蛋白（SarA和AgrA）之间有前景的相互作用，证实了它们的抗毒力和抗生物膜活性。这些发现表明，2,5-二酮哌嗪可能成为对抗抗生素耐药性的一种有前景的先导化合物。
