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Strategies for combating bacterial biofilms: A focus on anti-biofilm agents and their mechanisms of action

机译:对抗细菌生物膜的策略:关注抗生物膜剂及其作用机理

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摘要

ABSTRACT Biofilm refers to the complex, sessile communities of microbes found either attached to a surface or buried firmly in an extracellular matrix as aggregates. The biofilm matrix surrounding bacteria makes them tolerant to harsh conditions and resistant to antibacterial treatments. Moreover, the biofilms are responsible for causing a broad range of chronic diseases and due to the emergence of antibiotic resistance in bacteria it has really become difficult to treat them with efficacy. Furthermore, the antibiotics available till date are ineffective for treating these biofilm related infections due to their higher values of minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC), which may result in in-vivo toxicity. Hence, it is critically important to design or screen anti-biofilm molecules that can effectively minimize and eradicate biofilm related infections. In the present article, we have highlighted the mechanism of biofilm formation with reference to different models and various methods used for biofilm detection. A major focus has been put on various anti-biofilm molecules discovered or tested till date which may include herbal active compounds, chelating agents, peptide antibiotics, lantibiotics and synthetic chemical compounds along with their structures, mechanism of action and their respective MICs, MBCs, minimum biofilm inhibitory concentrations (MBICs) as well as the half maximal inhibitory concentration (IC50) values available in the literature so far. Different mode of action of anti biofilm molecules addressed here are inhibition via interference in the quorum sensing pathways, adhesion mechanism, disruption of extracellular DNA, protein, lipopolysaccharides, exopolysaccharides and secondary messengers involved in various signaling pathways. From this study, we conclude that the molecules considered here might be used to treat biofilm-associated infections after significant structural modifications, thereby investigating its effective delivery in the host. It should also be ensured that minimum effective concentration of these molecules must be capable of eradicating biofilm infections with maximum potency without posing any adverse side effects on the host.
机译:摘要生物膜是指复杂的,无柄的微生物群落,它们附着在表面或以团聚体的形式牢固地埋在细胞外基质中。细菌周围的生物膜基质使它们能够耐受恶劣条件并抵抗抗菌处理。此外,生物膜负责引起广泛的慢性疾病,并且由于细菌中抗生素耐药性的出现,实际上已经变得难以有效治疗它们。此外,迄今为止可用的抗生素由于其较高的最低抑菌浓度(MIC)和最低杀菌浓度(MBC)较高,因此无法有效治疗这些与生物膜相关的感染,这可能会导致体内毒性。因此,设计或筛选可有效减少和根除与生物膜有关的感染的抗生物膜分子至关重要。在本文中,我们参考了用于生物膜检测的不同模型和各种方法,重点介绍了生物膜形成的机制。迄今为止,人们一直将重点放在发现或测试的各种抗生物膜分子上,这些分子包括草药活性化合物,螯合剂,肽类抗生素,羊毛硫抗生素和合成化合物,以及它们的结构,作用机理及其各自的MIC,MBC,迄今为止,文献中提供的最小生物膜抑制浓度(MBIC)和最大抑制半浓度(IC 50 )的值。此处讨论的抗生物膜分子的不同作用方式是通过干扰群体感应途径,粘附机制,破坏细胞外DNA,蛋白质,脂多糖,胞外多糖和参与各种信号传导途径的次级信使而引起的抑制。根据这项研究,我们得出结论,此处考虑的分子在进行重大结构修饰后可用于治疗与生物膜相关的感染,从而研究其在宿主中的有效递送。还应确保这些分子的最小有效浓度必须能够以最大的效力消除生物膜感染,而不会对宿主造成任何不利的副作用。

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