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瑞帕菌素III与黏菌素联合对多重耐药鲍曼不动杆菌生物膜的体外抑制及根除作用

In vitro inhibition and eradication of multidrug-resistant Acinetobacter baumannii biofilms by riparin III and colistin combination.

作者信息

Oliveira Júnior Jorge Belém, Rocha da Mota Daivyane Aline, de Lima Fernanda Cristina Santos, Higino Taciana Mirely Maciel, Chavez Gutierrez Stanley Juan, Camara Celso Amorim, Barbosa Filho José Maria, Alves Luiz Carlos, Brayner Fábio André

机构信息

Laboratory of Molecular and Cellular Biology, Laboratory of Leishmaniasis and Mutagenesis, Department of Parasitology, Aggeu Magalhães Institute (FIOCRUZ/PE), Recife, Pernambuco, Brazil.

Laboratory of Molecular and Cellular Biology, Laboratory of Leishmaniasis and Mutagenesis, Department of Parasitology, Aggeu Magalhães Institute (FIOCRUZ/PE), Recife, Pernambuco, Brazil.

出版信息

Microb Pathog. 2023 Sep;182:106233. doi: 10.1016/j.micpath.2023.106233. Epub 2023 Jul 6.

Abstract

Acinetobacter baumannii, a prominent emerging pathogen, is responsible for persistent and recurrent healthcare-associated infections (HAIs). Its bacterial resistance and virulence factors, such as biofilm formation, contribute to its survival in hospital environments. Combination therapy has proven to be an effective approach for controlling these infections; however, antimicrobial resistance and compound toxicity can hinder antimicrobial efficacy. Numerous in vitro studies have demonstrated the synergistic effect of antimicrobials and natural products against multidrug-resistant (MDR) A. baumannii biofilm. Riparin III, a natural alkamide derived from Aniba riparia (Nees) Mez., possesses various biological activities, including significant antimicrobial potential. Nonetheless, no reports are available on the use of this compound in conjunction with conventional antimicrobials. Hence, this study aimed to investigate the inhibition and eradication of A. baumannii MDR biofilm by combining riparin III and colistin, along with potential ultrastructural changes observed in vitro. Clinical isolates of A. baumannii, known for their robust biofilm production, were inhibited, or eradicated in the presence of the riparin III/colistin combination. Furthermore, the combination resulted in several ultrastructural alterations within the biofilm, such as elongated cells and coccus morphology, partial or complete disruption of the biofilm's extracellular matrix, and cells exhibiting cytoplasmic material extravasation. At the synergistic concentrations, the riparin III/colistin combination exhibited a low hemolytic percentage, ranging from 5.74% to 6.19%, exerting inhibitory and eradicating effects on the A. baumannii biofilm, accompanied by notable ultrastructural changes. These findings suggest its potential as a promising alternative for therapeutic purposes.

摘要

鲍曼不动杆菌是一种突出的新兴病原体,可导致持续性和复发性医疗保健相关感染(HAIs)。其细菌耐药性和毒力因子,如生物膜形成,有助于其在医院环境中生存。联合治疗已被证明是控制这些感染的有效方法;然而,抗菌药物耐药性和化合物毒性可能会阻碍抗菌效果。大量体外研究表明,抗菌药物与天然产物对多重耐药(MDR)鲍曼不动杆菌生物膜具有协同作用。瑞帕林III是一种从巴西番荔枝(Nees)Mez.中提取的天然烷酰胺,具有多种生物活性,包括显著的抗菌潜力。尽管如此,关于该化合物与传统抗菌药物联合使用的报道尚未见。因此,本研究旨在探讨瑞帕林III与黏菌素联合对鲍曼不动杆菌MDR生物膜的抑制和根除作用,以及体外观察到的潜在超微结构变化。以其强大的生物膜产生能力而闻名的鲍曼不动杆菌临床分离株,在瑞帕林III/黏菌素联合存在的情况下受到抑制或根除。此外,该联合导致生物膜内出现多种超微结构改变,如细胞伸长和球菌形态、生物膜细胞外基质的部分或完全破坏,以及细胞出现细胞质物质外渗。在协同浓度下,瑞帕林III/黏菌素联合表现出较低的溶血百分比,范围为5.74%至6.19%,对鲍曼不动杆菌生物膜发挥抑制和根除作用,同时伴有显著的超微结构变化。这些发现表明其作为一种有前途的治疗替代方案的潜力。

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