Chattagul Supaksorn, Jackson Joseph, Wimley William C, Atreya Chintamani
Office of Blood Research and Review, Center for Biologics Evaluation and Research, Silver Spring, Maryland 20993, United States.
Department of Biochemistry and Molecular Biology, Tulane University School of Medicine, New Orleans, Louisiana 70112, United States.
ACS Infect Dis. 2025 Aug 8;11(8):2323-2330. doi: 10.1021/acsinfecdis.5c00363. Epub 2025 Jul 29.
With continuous improvements to blood donor deferrals and the availability of sensitive tests for donation screening for infectious agents, bacterial contamination of whole blood (WB) and blood components stored for transfusion is a rare event. Nonetheless, it still occurs and remains a transfusion-associated risk in terms of septic transfusion reactions (STRs) and transfusion-transmitted bacterial infections with morbidity and mortality outcomes. One of the risk mitigation strategies for bacterial contamination is to implement treatment with currently available proactive pathogen reduction technologies (PRTs) for these transfusion products. Here, as a proof of concept, we tested two recently developed unique cationic antimicrobial peptides (AMPs; D-CONGA and D-CONGA-Q7) for WB safety from bacterial contamination. In this study, WB was inoculated with and and treated with the two peptides to evaluate their bactericidal efficacy. The results demonstrated that D-CONGA and D-CONGA-Q7 exhibit potent inhibitory activity against the bacteria with a minimal inhibitory concentration (MIC) range of 4-8 and 1-8 μM, respectively, depending on the bacterial species tested. Time-kill kinetics further confirmed that the peptides exhibit bactericidal efficacy at 8 μM by achieving a 5-log reduction (99.999%) of the bacterial load in WB with a time-dependent killing profile. Furthermore, even at 20 μM, the AMPs did not negatively impact hemolysis or hemostatic properties. We have further demonstrated using a cationic exchange resin that the cationic AMPs can be separated and removed from WB after the peptide treatments. During 35-day WB storage at 2-8 °C, 4 μM D-CONGA-Q7 one-time treatment prevented growth and preserved WB quality and integrity. Overall, the results described here provide the first proof of concept that certain AMPs, such as D-CONGA and D-CONGA-Q7, can facilitate WB safety from bacteria during storage.
随着献血延期政策的不断完善以及用于献血筛查感染因子的灵敏检测方法的出现，全血（WB）和用于输血储存的血液成分的细菌污染是罕见事件。尽管如此，它仍会发生，并且就脓毒性输血反应（STRs）和具有发病和死亡后果的输血传播细菌感染而言，仍然是一种与输血相关的风险。减少细菌污染的风险缓解策略之一是对这些输血产品采用目前可用的主动病原体灭活技术（PRTs）进行处理。在此，作为概念验证，我们测试了两种最近开发的独特阳离子抗菌肽（AMPs；D-CONGA和D-CONGA-Q7）对WB预防细菌污染的安全性。在本研究中，将WB接种 和 并用这两种肽进行处理，以评估它们的杀菌效果。结果表明，D-CONGA和D-CONGA-Q7对细菌表现出强大的抑制活性，其最小抑菌浓度（MIC）范围分别为4-8 μM和1-8 μM，具体取决于所测试的细菌种类。时间-杀菌动力学进一步证实，这些肽在8 μM时通过使WB中的细菌载量呈时间依赖性杀灭曲线实现5个对数级的减少（99.999%），从而表现出杀菌效果。此外，即使在20 μM时，这些AMPs对溶血或止血特性也没有负面影响。我们进一步使用阳离子交换树脂证明，在肽处理后，阳离子AMPs可以从WB中分离并去除。在2-8°C下储存35天期间，4 μM D-CONGA-Q7一次性处理可防止 生长并保持WB的质量和完整性。总体而言，此处描述的结果提供了首个概念验证，即某些AMPs，如D-CONGA和D-CONGA-Q7，可在储存期间促进WB的细菌安全性。
