Eltayb Esra Kamal, Alqahtani Fulwah Yahya, Alkahtani Hamad M, Alsarra Ibrahim A, Alfaraj Rihaf, Aleanizy Fadilah Sfouq
Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh 11495, Saudi Arabia.
Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh 45142, Saudi Arabia.
Polymers (Basel). 2022 Sep 2;14(17):3655. doi: 10.3390/polym14173655.
contributes to many chronic infections and has been found to be resistant to multiple antibiotics. Pseudomonas use a quorum sensing system (QS) to control biofilm establishment and virulence factors, and, thus, quorum sensing inhibitors (QSIs), such as meta-bromo-thiolactone (mBTL), are promising anti-infective agents. Accordingly, this study intended to investigate the antibacterial and anti-virulence activity of mBTL-loaded calcium alginate nanoparticles (CANPs) against and different QS mutants. The results show that the mBTL-CANPs had higher antibacterial activity, which was made evident by decreases in all tested strains except the ∆lasR/∆rhlR double mutant, with MIC (0.5 mg/mL) of mBTL-CANPs compared with free mBTL at MIC (˃1 mg/mL). The biofilm formation of and some QS-deficient mutants were reduced in response to 0.5-0.125 mg/mL of mBTL-encapsulating CANPs. The pyocyanin production of the tested strains except ∆lasA and ∆rhlR decreased when challenged with 0.5 mg/mL of mBTL-loaded NPs. The subsequent characterization of the cytotoxic effect of these NPs on human lung epithelial cells (A549) and cystic fibrosis fibroblast cells (LL 29) demonstrated that synthesized NPs were cytocompatible at MIC in both cell lines and markedly reduced the cytotoxic effect observed with mBTL alone on these cells. The resulting formulation reduced the strains' adhesion to A549 comparably with mBTL, suggesting their potential anti-adhesive effect. Given the virulence suppressing action, cytocompatibility, and enhanced anti-biofilm effect of mBTL-CANPs, and the advantage of alginate-based NPs as an antimicrobial delivery system these nanoparticles have great potential in the prophylaxis and treatment of infection caused by .
它导致许多慢性感染，并且已被发现对多种抗生素具有抗性。铜绿假单胞菌利用群体感应系统（QS）来控制生物膜的形成和毒力因子，因此，群体感应抑制剂（QSIs），如间溴硫内酯（mBTL），是很有前景的抗感染剂。因此，本研究旨在研究负载mBTL的海藻酸钙纳米颗粒（CANPs）对不同QS突变体的抗菌和抗毒力活性。结果表明，mBTL-CANPs具有更高的抗菌活性，除∆lasR/∆rhlR双突变体外，所有测试菌株的数量均减少，这表明了其抗菌活性，mBTL-CANPs的最低抑菌浓度（MIC）为0.5mg/mL，而游离mBTL的MIC为˃1mg/mL。0.5-0.125mg/mL的包裹mBTL的CANPs可减少铜绿假单胞菌和一些QS缺陷突变体的生物膜形成。当用0.5mg/mL负载mBTL的纳米颗粒攻击时，除∆lasA和∆rhlR外，测试菌株的绿脓菌素产量下降。随后对这些纳米颗粒对人肺上皮细胞（A549）和囊性纤维化成纤维细胞（LL 29）的细胞毒性作用进行表征，结果表明合成的纳米颗粒在两种细胞系的MIC浓度下具有细胞相容性，并显著降低了单独使用mBTL时对这些细胞观察到的细胞毒性作用。所得制剂与mBTL相比，同等程度地降低了铜绿假单胞菌菌株对A549的粘附，表明其具有潜在的抗粘附作用。鉴于mBTL-CANPs的毒力抑制作用、细胞相容性和增强的抗生物膜作用，以及基于海藻酸盐的纳米颗粒作为抗菌递送系统的优势，这些纳米颗粒在预防和治疗由铜绿假单胞菌引起的感染方面具有巨大潜力。
