Muteeb Ghazala, Rehman Md Tabish, Ali Saeedut Zafar, Al-Shahrani Abdurrahman M, Kamal Mohammad Amjad, Ashraf Ghulam Md
Department of Medical Lab. Sciences, College of Applied Medical Science, Wadi Al Dawasir, Prince Sattam bin Abdulaziz University. Saudi Arabia.
Department of Pharmacognosy, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh, 11451. Saudi Arabia.
Curr Drug Metab. 2017;18(2):90-95. doi: 10.2174/1389200217666160727100434.
The emergence of antibiotic resistance in bacteria is a serious threat with enormous social and economic implications. The distribution of resistance genes/markers through horizontal gene transfer leads to the dissemination of resistant strains in different parts of the world. The resistant bacteria acquire the ability to overcome resistance by different modes amongst which the expression of β-lactamases is a major factor. The β-lactamase enzymes cleave the amide bond of the β-lactam antibiotics, which constitute about one-third of the antibiotics used all over the world. In a quest to control the spread of resistant bacteria, advanced generations of antibiotics are used either alone or in combination with inhibitors. However, these antibiotics and inhibitors also contain β-lactam ring in their structure and hence are prone to be hydrolyzed by β-lactamase enzymes in the near future. Thus, the severity of the problem is manifested due to the paucity of novel non-β-lactam core containing antibiotics in the drug development stage. One approach to overcome these shortcomings is to use peptide-based inhibitors. Here, we describe the potential use of phage display technique to screen commercially available libraries to pan against β-lactamase enzymes. The main advantage of using peptide-based inhibitors is that the bacteria will not be able to recruit pre-existing defense mechanisms and it will take a long time to evolve a new mechanism in its defense against peptide-based inhibitors.
细菌中抗生素耐药性的出现是一个严重威胁，具有巨大的社会和经济影响。耐药基因/标记通过水平基因转移进行传播，导致耐药菌株在世界不同地区扩散。耐药细菌通过不同方式获得克服耐药性的能力，其中β-内酰胺酶的表达是一个主要因素。β-内酰胺酶可裂解β-内酰胺抗生素的酰胺键，β-内酰胺抗生素约占全球使用抗生素的三分之一。为了控制耐药细菌的传播，新一代抗生素单独使用或与抑制剂联合使用。然而，这些抗生素和抑制剂的结构中也含有β-内酰胺环，因此在不久的将来容易被β-内酰胺酶水解。因此，由于药物研发阶段新型非β-内酰胺核心抗生素的匮乏，问题的严重性凸显出来。克服这些缺点的一种方法是使用基于肽的抑制剂。在此，我们描述了利用噬菌体展示技术筛选市售文库以筛选针对β-内酰胺酶的潜在用途。使用基于肽的抑制剂的主要优点是细菌无法调用预先存在的防御机制，并且细菌需要很长时间才能进化出针对基于肽的抑制剂的新防御机制。
