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Targeted Anti Bacterial Therapy

机译：靶向抗细菌治疗

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The increasing development of bacterial resistance to traditional antibiotics has reached alarming levels, thus necessitating a strong need to develop new antimicrobial agents. These new antimicrobials should possess novel modes of action and/or different cellular targets compared with the existing antibiotics. As a result, new classes of compounds designed to avoid defined resistance mechanisms are undergoing pre clinical and clinical evaluation. Microbial and phage genomic sequencing are now being used to find previously unidentified genes and their corresponding proteins. In both traditional and newly developed antibiotics, the target selectivity lies in the drug itself, in its ability to affect a mechanism that is unique to prokaryotes. As a result, a vast number of potent agents that, due to low selectivity, in addition to the pathogen also affect the eukaryote host have been excluded from use as therapeutics. Such compounds could be re-considered for clinical use if applied as part of a targeted delivery platform where the drug selectivity is replaced by targetselectivity borne by the targeting moiety.nnWith a large number of antibodies and antibody-drug conjugates already approved or near approval as cancer therapeutics, targeted therapy is becoming increasingly attractive and additional potential targeting moieties that are non-antibody based, such as peptides, nonantibody ligand-binding proteins and even carbohydrates are receiving increasing attention. Still, targeted therapy is mostly focused on cancer, with targeted anti bacterial therapies being suggested only very recently. This review will focus in the various methods of antimicrobial targeting, by systemic and local application of targeted antimicrobial substances.
机译：细菌对传统抗生素的抗药性日益增长，已达到令人震惊的水平，因此迫切需要开发新的抗菌剂。与现有抗生素相比，这些新的抗菌药物应具有新颖的作用方式和/或不同的细胞靶标。结果，旨在避免确定的耐药机制的新型化合物正在接受临床前和临床评估。微生物和噬菌体基因组测序现已用于发现先前未鉴定的基因及其相应的蛋白质。在传统抗生素和新开发的抗生素中，靶标选择性都取决于药物本身，其影响原核生物独特机制的能力。结果，由于病原体的低选择性，除病原菌外还影响真核生物宿主的大量有效药物已被排除在治疗药物之外。如果将这类化合物用作靶向传递平台的一部分，则可以重新考虑将其用于临床，在该平台中，药物选择性被靶向部分所承担的靶选择性所取代。nn大量的抗体和抗体-药物偶联物已获批准或接近批准。在癌症治疗中，靶向治疗变得越来越有吸引力，并且其他非基于抗体的潜在靶向部分（例如肽，非抗体配体结合蛋白，甚至碳水化合物）也越来越受到关注。尽管如此，靶向治疗仍主要集中在癌症上，仅在最近才提出靶向抗细菌治疗。这篇综述将着重于通过靶向性抗菌物质的系统性和局部性应用来靶向抗菌的各种方法。

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