Meliefste Henriëtte Margarethe, Mudde Saskia Emily, Ammerman Nicole Christine, de Steenwinkel Jurriaan Evert M, Bax Hannelore Iris
Department of Medical Microbiology and Infectious Diseases, Erasmus University Medical Center, Rotterdam, Netherlands.
Department of Internal Medicine, Section of Infectious Diseases, Erasmus University Medical Center, Rotterdam, Netherlands.
Front Microbiol. 2024 Apr 16;15:1392606. doi: 10.3389/fmicb.2024.1392606. eCollection 2024.
is an emerging opportunistic pathogen causing severe pulmonary infections in patients with underlying lung disease and cystic fibrosis in particular. The rising prevalence of infections poses an alarming threat, as the success rates of available treatment options are limited. Central to this challenge is the absence of preclinical models that accurately mimic conditions and that can reliably predict treatment outcomes in patients. is notorious for its association with biofilm formation within the lung. Bacteria in biofilms are more recalcitrant to antibiotic treatment compared to planktonic bacteria, which likely contributes to the lack of correlation between preclinical drug activity testing (typically performed on planktonic bacteria) and treatment outcome. In recent years, there has been a growing interest in biofilm research. However, the absence of standardized methods for biofilm culture, biofilm characterization and drug activity testing has led to a wide spectrum of, sometimes inconsistent, findings across various studies. Factors such as strain selection, culture medium, and incubation time hugely impact biofilm development, phenotypical characteristics and antibiotic susceptibility. Additionally, a broad range of techniques are used to study biofilms, including quantification of colony-forming units, crystal violet staining and fluorescence microscopy. Yet, limitations of these techniques and the selected readouts for analysis affect study outcomes. Currently, research on the activity of conventional antibiotics, such as clarithromycin and amikacin, against biofilms yield ambiguous results, underscoring the substantial impact of experimental conditions on drug activity assessment. Beyond traditional drug activity testing, the exploration of novel anti-biofilm compounds and the improvement of biofilm models are ongoing. In this review, we outline the laboratory models, experimental variables and techniques that are used to study biofilms. We elaborate on the current insights of biofilm characteristics and describe the present understanding of the activity of traditional antibiotics, as well as potential novel compounds, against biofilms. Ultimately, this work contributes to the advancement of fundamental knowledge and practical applications of accurate preclinical models, thereby facilitating progress towards improved therapies for infections.
是一种新兴的机会致病菌，尤其在患有基础肺部疾病，特别是囊性纤维化的患者中引起严重的肺部感染。感染患病率的上升构成了令人担忧的威胁，因为现有治疗方案的成功率有限。这一挑战的核心在于缺乏能够准确模拟病情并可靠预测患者治疗结果的临床前模型。因其与肺部生物膜形成有关而声名狼藉。与浮游细菌相比，生物膜中的细菌对抗生素治疗更具抗性，这可能是临床前药物活性测试（通常针对浮游细菌进行）与治疗结果缺乏相关性的原因。近年来，对生物膜研究的兴趣日益浓厚。然而，生物膜培养、生物膜表征和药物活性测试缺乏标准化方法，导致各项研究结果范围广泛，有时甚至不一致。菌株选择、培养基和孵育时间等因素对生物膜的形成、表型特征和抗生素敏感性有巨大影响。此外，广泛使用各种技术来研究生物膜，包括菌落形成单位的定量、结晶紫染色和荧光显微镜检查。然而，这些技术的局限性以及所选的分析读数会影响研究结果。目前，关于克拉霉素和阿米卡星等传统抗生素对生物膜活性的研究结果不明确，凸显了实验条件对药物活性评估的重大影响。除了传统的药物活性测试外，新型抗生物膜化合物的探索和生物膜模型的改进也在进行中。在这篇综述中，我们概述了用于研究生物膜的实验室模型、实验变量和技术。我们详细阐述了目前对生物膜特征的认识，并描述了目前对传统抗生素以及潜在新型化合物对生物膜活性的理解。最终，这项工作有助于推进准确临床前模型的基础知识和实际应用，从而促进针对感染的治疗取得进展。
