Iannuzo Natalie, Haller Yannik A, McBride Michelle, Mehari Sabrina, Lainson John C, Diehnelt Chris W, Haydel Shelley E
School of Life Sciences, Arizona State University, Tempe, Arizona 85287, United States.
School of Molecular Sciences, Arizona State University, Tempe, Arizona 85287, United States.
ACS Omega. 2022 Jun 27;7(27):23967-23977. doi: 10.1021/acsomega.2c02844. eCollection 2022 Jul 12.
The rise in antibiotic resistance in bacteria has spawned new technological approaches for identifying novel antimicrobials with narrow specificity. Current antibiotic treatment regimens and antituberculosis drugs are not effective in treating . Meanwhile, antimicrobial peptides are gaining prominence as alternative antimicrobials due to their specificity toward anionic bacterial membranes, rapid action, and limited development of resistance. To rapidly identify antimicrobial peptide candidates, our group has developed a high-density peptide microarray consisting of 125,000 random synthetic peptides screened for interaction with the mycobacterial cell surface of morphotypes. From the array screening, peptides positive for interaction were synthesized and their antimicrobial activity was validated. Overall, six peptides inhibited the smooth morphotype (IC = 1.7 μM for all peptides) and had reduced activity against the rough morphotype (IC range: 13-82 μM). Peptides ASU2056 and ASU2060 had minimum inhibitory concentration values of 32 and 8 μM, respectively, against the smooth morphotype. Additionally, ASU2060 (8 μM) was active against , including multidrug-resistant clinical isolates, , and methicillin-resistant . ASU2056 and ASU2060 exhibited no significant hemolytic activity at biologically relevant concentrations, further supporting these peptides as promising therapeutic candidates. Moreover, ASU2060 retained antibacterial activity after preincubation in human serum for 24 h. With antimicrobial resistance on the rise, methods such as those presented here will streamline the peptide discovery process for targeted antimicrobial peptides.
细菌中抗生素耐药性的增加催生了用于鉴定具有窄特异性的新型抗菌剂的新技术方法。目前的抗生素治疗方案和抗结核药物在治疗……方面无效。与此同时，抗菌肽因其对阴离子细菌膜的特异性、快速作用以及有限的耐药性发展而作为替代抗菌剂受到关注。为了快速鉴定抗菌肽候选物，我们小组开发了一种高密度肽微阵列，该阵列由125,000种随机合成肽组成，筛选它们与……形态型的分枝杆菌细胞表面的相互作用。通过阵列筛选，合成了相互作用呈阳性的肽，并验证了它们的抗菌活性。总体而言，六种肽抑制……光滑形态型（所有肽的IC = 1.7 μM），而对……粗糙形态型的活性降低（IC范围：13 - 82 μM）。肽ASU2056和ASU2060对……光滑形态型的最低抑菌浓度值分别为32 μM和8 μM。此外，ASU2060（8 μM）对……有活性，包括多重耐药的……临床分离株、……和耐甲氧西林的……。ASU2056和ASU2060在生物学相关浓度下没有显著的溶血活性，进一步支持这些肽作为有前景的治疗候选物。此外，ASU2060在人血清中预孵育24小时后仍保留抗菌活性。随着抗菌耐药性的增加，本文介绍的方法等将简化靶向抗菌肽的肽发现过程。
