聚羟基丁酸纳米颗粒提高铜绿假单胞菌对头孢曲松的敏感性并减少体外生物膜形成。

Polyhydroxybutyrate nanoparticle improving the sensitivity of Pseudomonas aeruginosa to ceftriaxone and reducing the biofilm formation in vitro.

作者信息

Sadiq Shams Ihssan, Ghafil Jenan Atiyah

机构信息

Department of Biology, College of Science, University of Baghdad, Iraq.

出版信息

Polim Med. 2025 Jan-Jun;55(1):31-37. doi: 10.17219/pim/203765.

DOI:10.17219/pim/203765

PMID:40599100

Abstract

BACKGROUND

Polyhydroxybutyrate nanoparticles (PHB-NPs) represent a promising strategy for addressing the growing threat of bacterial resistance to antibiotics - a major concern in global public health. Despite their potential, there is a noticeable gap in the current literature regarding their ability to enhance the efficacy of existing antibiotic therapies.

OBJECTIVES

This study investigates the synergistic effect of PHB-NPs in enhancing the antibacterial activity of ceftriaxone (CRO) against Pseudomonas aeruginosa, with a particular focus on mitigating key virulence factors such as biofilm formation and adhesion.

MATERIAL AND METHODS

Polyhydroxybutyrate nanoparticles were synthesized using the pH gradient and sonication method. The antibacterial activity of PHB-NPs, CRO and the combined formulation (PHB-NP-CRO) was assessed using minimum inhibitory concentration (MIC) testing and the well diffusion method. Additionally, the effects of these formulations on P. aeruginosa biofilm formation on an abiotic surface (polystyrene) and bacterial adhesion to human oral mucosal epithelial cells (OMECs) were evaluated.

RESULTS

The diameters of the prepared PHB-NPs ranged from 15 nm to 34 nm, with an average size of 28.2 ±6.3 nm. All P. aeruginosa isolates were capable of biofilm production. A negative correlation was observed between the diameter of the CRO inhibition zones and the extent of biofilm formation among the 20 isolates. The MICs for PHB, PHB-NPs, CRO, and the combined formulation (PHB-NP-CRO) were 2,000, 1,000, 250, and 62.5 μg/mL, respectively. Sub-MIC concentrations (as low as 1/32 MIC) of both CRO and PHB-NP-CRO exhibited significant inhibitory effects on biofilm formation and bacterial adhesion to human OMECs (p < 0.050).

CONCLUSIONS

The combination of PHB-NPs with CRO significantly enhances the antibacterial activity of CRO against P. aeruginosa. Moreover, sub-inhibitory concentrations (sub-MICs) of both PHB-NP-CRO and CRO alone effectively reduce the bacterium's ability to form biofilms and adhere to biotic surfaces.

摘要

背景

聚羟基丁酸酯纳米颗粒（PHB-NPs）是应对细菌对抗生素耐药性这一日益严重威胁的一种有前景的策略，而细菌耐药性是全球公共卫生领域的一个主要担忧。尽管它们具有潜力，但目前关于其增强现有抗生素疗法疗效能力的文献存在明显空白。

目的

本研究调查了PHB-NPs在增强头孢曲松（CRO）对铜绿假单胞菌抗菌活性方面的协同作用，特别关注减轻生物膜形成和黏附等关键毒力因子。

材料与方法

采用pH梯度和超声法合成聚羟基丁酸酯纳米颗粒。使用最低抑菌浓度（MIC）测试和琼脂扩散法评估PHB-NPs、CRO及联合制剂（PHB-NP-CRO）的抗菌活性。此外，评估了这些制剂对铜绿假单胞菌在非生物表面（聚苯乙烯）形成生物膜及细菌黏附于人口腔黏膜上皮细胞（OMECs）的影响。

结果

制备的PHB-NPs直径范围为15nm至34nm，平均尺寸为28.2±6.3nm。所有铜绿假单胞菌分离株均能产生生物膜。在20株分离株中，观察到CRO抑菌圈直径与生物膜形成程度之间呈负相关。PHB、PHB-NPs、CRO及联合制剂（PHB-NP-CRO）的MIC分别为2000、1000、250和62.5μg/mL。CRO和PHB-NP-CRO的亚MIC浓度（低至1/32 MIC）对生物膜形成及细菌黏附于人OMECs均表现出显著抑制作用（p<0.050）。