Treatment of pneumococcal infections is limited by antibiotic resistance and exacerbation of disease by bacterial lysis releasing pneumolysin toxin and other inflammatory factors. We identified a previously uncharacterized peptide in the Klebsiella pneumoniae secretome, which enters Streptococcus pneumoniae via its AmiA-AliA/AliB permease. Subsequent downregulation of genes for amino acid biosynthesis and peptide uptake was associated with reduction of pneumococcal growth in defined medium and human cerebrospinal fluid, irregular cell shape, decreased chain length and decreased genetic transformation. The bacteriostatic effect was specific to S. pneumoniae and Streptococcus pseudopneumoniae with no effect on Streptococcus mitis, Haemophilus influenzae, Staphylococcus aureus or K. pneumoniae. Peptide sequence and length were crucial to growth suppression. The peptide reduced pneumococcal adherence to primary human airway epithelial cell cultures and colonization of rat nasopharynx, without toxicity. We identified a peptide with potential as a therapeutic for pneumococcal diseases suppressing growth of multiple clinical isolates, including antibiotic resistant strains, while avoiding bacterial lysis and dysbiosis.

肺炎球菌感染的治疗受到抗生素耐药性以及细菌溶解释放肺炎球菌溶血素毒素和其他炎症因子导致疾病恶化的限制。我们在肺炎克雷伯菌分泌组中发现了一种以前未表征的肽，它通过其 AmiA-AliA/AliB 通透酶进入肺炎链球菌。随后氨基酸生物合成和肽摄取基因的下调与特定培养基和人脑脊液中肺炎球菌生长的减少、细胞形状不规则、链长度缩短和遗传转化减少有关。对肺炎链球菌和假肺炎链球菌具有特异性抑菌作用，对轻症链球菌、流感嗜血杆菌、金黄色葡萄球菌或肺炎克雷伯菌没有作用。肽序列和长度对于生长抑制至关重要。该肽可减少肺炎球菌对原代人气道上皮细胞培养物的粘附和大鼠鼻咽部的定植，且无毒性。我们发现了一种具有治疗肺炎球菌疾病潜力的肽，可抑制多种临床分离株（包括抗生素耐药菌株）的生长，同时避免细菌裂解和生态失调。