Vaňková Eva, Lokočová Kristýna, Kašparová Petra, Hadravová Romana, Křížová Ivana, Maťátková Olga, Masák Jan, Šícha Václav
Department of Biotechnology, University of Chemistry and Technology Prague, Technická 5, 166 28 Prague, Czech Republic.
Institute of Organic Chemistry and Biochemistry of the Czech Academy of Sciences, Flemingovo náměstí 542/2, 166 10 Prague, Czech Republic.
Pharmaceuticals (Basel). 2022 Apr 26;15(5):534. doi: 10.3390/ph15050534.
The emergence of antibiotic resistance in opportunistic pathogens represents a huge problem, the solution for which may be a treatment with a combination of multiple antimicrobial agents. Sodium salt of cobalt bis-dicarbollide (COSAN.Na) is one of the very stable, low-toxic, amphiphilic boron-rich sandwich complex heteroboranes. This compound has a wide range of potential applications in the biological sciences due to its antitumor, anti-HIV-1, antimicrobial and antibiofilm activity. Our study confirmed the ability of COSAN.Na (in the concentration range 0.2-2.48 µg/mL) to enhance tetracycline, erythromycin, and vancomycin action towards planktonic growth with an additive or synergistic effect (e.g., the combination of 1.24 µg/mL COSAN.Na and 6.5 µg/mL TET). The effective inhibitory concentration of antibiotics was reduced up to tenfold most efficiently in the case of tetracycline (from 65 to 6.5 µg/mL). In addition, strong effect of COSAN.Na on disruption of the cell envelopes was determined using propidium iodide uptake measurement and further confirmed by transmission electron microscopy. The combination of amphiphilic COSAN.Na with antibiotics can therefore be considered a promising way to overcome antibiotic resistance in Gram-positive cocci.
机会性病原体中抗生素耐药性的出现是一个巨大的问题，解决这一问题的方法可能是联合使用多种抗菌药物进行治疗。双二碳硼烷钴钠盐（COSAN.Na）是一种非常稳定、低毒的两亲性富硼夹心络合物杂硼烷。由于其具有抗肿瘤、抗HIV-1、抗菌和抗生物膜活性，该化合物在生物科学领域具有广泛的潜在应用。我们的研究证实了COSAN.Na（浓度范围为0.2-2.48µg/mL）能够增强四环素、红霉素和万古霉素对浮游生长的作用，具有相加或协同效应（例如，1.24µg/mL COSAN.Na与6.5µg/mL四环素的组合）。在四环素的情况下，抗生素的有效抑制浓度最有效地降低了十倍（从65µg/mL降至6.5µg/mL）。此外，通过碘化丙啶摄取测量确定了COSAN.Na对细胞膜破坏的强烈作用，并通过透射电子显微镜进一步证实。因此，两亲性COSAN.Na与抗生素的组合可被视为克服革兰氏阳性球菌抗生素耐药性的一种有前景的方法。
