Animal histological images for <em>in vivo</em> maximum tolerated dose and toxicity

The rising rate of antibiotic resistance is a widely acknowledged challenge, especially for gram-negative bacterial infections. Some drugs, such as the lipopeptide polymyxin B (PMB), have high antimicrobial activity against gram-negative organisms but also high toxicity owing to low specificity, resulting in a low therapeutic index and poor clinical utility. Due to the high rate of nephrotoxicity, systemic use of PMB is presently restricted to last-line therapy, with adverse clinical tradeoffs. To salvage such antibiotics, we propose specific drug delivery to bacterial cells using engineered phage as a carrier. We replaced the receptor-binding protein of phage M13 with an antibody fragment (scFab) recognizing the core antigen of lipopolysaccharide (LPS), creating a phage that bound a wide range of clinically important gram-negative pathogen species. We then cross-linked thousands of PMB molecules per virion, making ‘PMB-Phage’. PMB-Phage reduced the minimum inhibitory concentration (MIC..., , , README: Animal histological images for *in vivo* maximum tolerated dose and toxicity Associated article: Yang Y, Vexler S, Jordan MC, et al. “A Synthetic Phage-Peptide Conjugate as a Potent Antibacterial Agent for Pseudomonas aeruginosa Infections.” ACS Central Science. DOI: 10.1021/acscentsci.5c00562 Contact: Irene A. Chen — [[e-mail]](mailto:[e-mail]) License: Data are released by Dryad under CC0 (public domain). 1\) Summary This dataset contains whole-slide histology images from a 7-day in vivo maximum tolerated dose (MTD) / toxicity study in mice exposed to polymyxin B (PMB), engineered phage–peptide conjugate (PMB-M13αLPS), 1× PBS vehicle, or no injection. For each animal, formalin-fixed, paraffin-embedded tissues (kidney, liver, spleen) were H&E-stained and scanned as whole-slide images. Slides were labeled so that the pathologist was blinded to treatment. The dataset is intended to enable independent inspection of tissue morphology for treatment-related...,抗生素耐药性的上升是全球公认的严峻挑战，尤以革兰氏阴性（Gram-negative）细菌感染为甚。部分药物，如脂肽类多粘菌素B（polymyxin B, PMB），对革兰氏阴性菌具备强效抗菌活性，但因特异性低下而毒性较强，导致治疗指数偏低、临床应用受限。鉴于其肾毒性发生率较高，目前多粘菌素B的全身给药仅被限定作为最后一线治疗方案，且临床应用需权衡显著的不良反应。为挽救这类抗生素，我们提出以工程化噬菌体作为载体，实现靶向细菌细胞的药物递送。我们将M13噬菌体的受体结合蛋白替换为识别脂多糖（lipopolysaccharide, LPS）核心抗原的抗体片段（scFab），构建出可结合多种临床重要革兰氏阴性病原菌的重组噬菌体。随后我们在每个病毒颗粒上交联数千个PMB分子，制备得到"PMB-噬菌体"复合物。PMB-噬菌体可降低最低抑菌浓度（minimum inhibitory concentration, MIC）…… README：用于*体内*最大耐受剂量与毒性研究的动物组织学图像 相关研究论文：Yang Y、Vexler S、Jordan MC 等，《合成噬菌体-肽偶联物作为铜绿假单胞菌感染的强效抗菌剂》，发表于*ACS Central Science*，DOI: 10.1021/acscentsci.5c00562 联系方式：Irene A. Chen — <a href="mailto:[e-mail]">[e-mail]</a> 授权协议：本数据集由Dryad平台以CC0（公共领域）协议发布。 1）研究摘要：本数据集包含7天*体内*最大耐受剂量（maximum tolerated dose, MTD）与毒性研究的全视野组织学图像，实验对象为分别暴露于多粘菌素B（PMB）、工程化噬菌体-肽偶联物（PMB-M13αLPS）、1倍磷酸盐缓冲生理盐水（phosphate-buffered saline, PBS）载体，或未接受注射的小鼠。对每只实验动物的福尔马林固定石蜡包埋组织（肾脏、肝脏、脾脏）进行苏木精-伊红（H&E）染色，并扫描为全视野数字图像。实验人员对玻片进行了标注处理，以实现病理学家的盲法阅片。本数据集旨在支持对治疗相关组织形态学变化的独立评估……