Dipartimento di Patologia Sperimentale, Biotecnologie Mediche, Infettivologia ed Epidemiologia, University of Pisa, Pisa, Italy.
Curr Med Chem. 2011;18(2):256-79. doi: 10.2174/092986711794088399.
The formation of surface-attached cellular agglomerates, the so-called biofilms, contributes significantly to bacterial resistance to antibiotics and innate host defenses. Bacterial biofilms are associated to various pathological conditions in humans such as cystic fibrosis, colonization of indwelling medical devices and dental plaque formation involved in caries and periodontitis. Over the last years, natural antimicrobial peptides (AMPs) have attracted considerable interest as a new class of antimicrobial drugs for a number of reasons. Among these, there are the broad activity spectrum, the relative selectivity towards their targets (microbial membranes), the rapid mechanism of action and, above all, the low frequency in selecting resistant strains. Since biofilm resistance to antibiotics is mainly due to the slow growth rate and low metabolic activity of bacteria in such community, the use of AMPs to inhibit biofilm formation could be potentially an attractive therapeutic approach. In fact, due to the prevalent mechanism of action of AMPs, which relies on their ability to permeabilize and/or to form pores within the cytoplasmic membranes, they have a high potential to act also on slow growing or even non-growing bacteria. This review will highlight the most important findings obtained testing AMPs in in vitro and in vivo models of bacterial biofilms, pointing out the possible advantages and limits of their use against microbial biofilm-related infections.
表面附着的细胞聚集体(即生物膜)的形成极大地促进了细菌对抗生素和固有宿主防御的抵抗力。细菌生物膜与人类的各种病理状况有关,如囊性纤维化、留置医疗设备的定植以及与龋齿和牙周炎有关的牙菌斑形成。近年来,天然抗菌肽 (AMP) 因其多种原因引起了人们的极大兴趣,成为一类新的抗菌药物。其中,广谱活性、对其靶标(微生物膜)的相对选择性、快速作用机制以及最重要的是选择耐药菌株的频率低。由于生物膜对抗生素的耐药性主要是由于此类群落中细菌的生长速度慢和代谢活性低,因此使用 AMP 抑制生物膜形成可能是一种有吸引力的治疗方法。事实上,由于 AMP 的作用机制普遍依赖于它们穿透和/或在细胞质膜内形成孔的能力,因此它们对生长缓慢甚至不生长的细菌也具有很高的作用潜力。这篇综述将重点介绍在细菌生物膜的体外和体内模型中测试 AMP 时获得的最重要发现,指出针对微生物生物膜相关感染使用 AMP 的可能优势和限制。