Sela Uri, Heselpoth Ryan D, Fischetti Vincent A
Laboratory of Bacterial Pathogenesis and Immunology, The Rockefeller University, 1230 York Avenue, New York, NY 10065, USA.
Antibiotics (Basel). 2025 Mar 27;14(4):344. doi: 10.3390/antibiotics14040344.
: Acne vulgaris is a skin disorder that affects millions worldwide, with playing a key role in its inflammation. Antibiotics reduce and inflammation, but growing antibiotic resistance has limited their efficacy. Additionally, other common acne treatments with bactericidal activity, like benzoyl peroxide, cause irritation, dryness, and peeling. To fulfill the unmet need for alternative therapies, our strategy focused on identifying potent phage lysins and/or their derived cationic peptides. : The C-terminal cationic antimicrobial peptide of the phage lysin PlyPi01 was synthesized along with several sequence-engineered variants in an attempt to enhance their bactericidal efficacy. In vitro bacterial killing assays evaluated the potency of the lysin-derived peptide derivatives against and , another skin bacterium associated with acne. Antibacterial activity was assessed both in conditions simulating the human skin and in combination with retinoids. : The variant peptide P156 was engineered by adding arginine residues at both the N- and C-terminal ends of the parental peptide PiP01. P156 was highly potent and eradicated all tested strains of and . P156 acted rapidly (>5-log kill in 10 min), further reducing the potential of resistance development. Additionally, P156 maintained its potency under conditions (e.g., temperature, pH, and salt concentration) observed on the skin surface and in hair follicles, as well as in combination with retinoid-all without being toxic to human cells. : These collective findings position P156 as a promising topical drug for clinical applications to control acne vulgaris.
寻常痤疮是一种影响全球数百万人的皮肤疾病，[某种物质]在其炎症过程中起关键作用。抗生素可减少[相关物质]并减轻炎症，但日益增长的抗生素耐药性限制了它们的疗效。此外，其他具有杀菌活性的常见痤疮治疗药物，如过氧化苯甲酰，会引起刺激、干燥和脱皮。为了满足对替代疗法的未满足需求，我们的策略集中在鉴定有效的噬菌体溶素和/或其衍生的阳离子肽。：合成了噬菌体溶素PlyPi01的C端阳离子抗菌肽以及几种经过序列工程改造的变体，以提高它们的杀菌效力。体外细菌杀伤试验评估了溶素衍生肽衍生物对[某种细菌]和[痤疮相关的另一种皮肤细菌]的效力。在模拟人体皮肤的条件下以及与维甲酸联合使用时评估了抗菌活性。：变体肽P156是通过在亲本肽PiP01的N端和C端都添加精氨酸残基而设计的。P156非常有效，能根除所有测试的[某种细菌]和[另一种细菌]菌株。P156作用迅速（10分钟内杀灭>5个对数级），进一步降低了耐药性产生的可能性。此外，P156在皮肤表面和毛囊中观察到的条件（如温度、pH值和盐浓度）下以及与维甲酸联合使用时都保持其效力，而且对人体细胞无毒。：这些综合发现使P156成为用于临床控制寻常痤疮的一种有前景的局部用药。
