Monsibais Alisha N, Tea Olivia, Ghatbale Pooja, Dunham Sage J B, Zünd Mirjam, Phan Jennifer, Lam Karen, Paulson McKenna, Tran Natalie, Suder Diana S, Blanc Alisha N, Samillano Cyril, Suh Joy, Atif Hanna, Vien Ethan, Nguyen Ryan, Vo Allene, Gonen Shane, Pride David, Whiteson Katrine
Department of Molecular Biology and Biochemistry, University of California Irvine, Irvine, California, USA.
Department of Pathology, University of California San Diego, La Jolla, California, USA.
Antimicrob Agents Chemother. 2025 Mar 5;69(3):e0116224. doi: 10.1128/aac.01162-24. Epub 2025 Jan 22.
is an understudied, gram-negative, aerobic bacterium that is widespread in the environment and increasingly a cause of opportunistic infections. Treating remains difficult, leading to an increase in disease severity and higher hospitalization rates in people with cystic fibrosis, cancer, and other immunocompromised health conditions. The lack of effective antibiotics has led to renewed interest in phage therapy; however, there remains a great need for well-characterized phages, especially against . In response to an oncology patient with a sepsis infection, we collected 18 phages from Southern California wastewater influent that exhibit different plaque morphology against host strain B28B. We hypothesized that, when combined into a cocktail, genetically diverse phages would give rise to distinct lytic infection kinetics that would enhance bacterial killing when compared to the individual phages alone. We identified three genetically distinct clusters of phages, and a representative from each group was further investigated and screened for potential therapeutic use. The results demonstrated that the three-phage cocktail significantly suppressed bacterial growth compared with individual phages when observed for 48 h. We also assessed the lytic impacts of our three-phage cocktail against a collection of 46 . strains to determine if a multi-phage cocktail has an expanded host range. Our phages remained strain-specific and infected >50% of tested strains. In six clinically relevant strains, the multi-phage cocktail has enhanced suppression of bacterial growth. These findings suggest that specialized phage cocktails may be an effective avenue of treatment for recalcitrant infections resistant to current antibiotics.
是一种研究较少的革兰氏阴性需氧细菌，广泛存在于环境中，越来越多地成为机会性感染的病因。治疗仍然困难，导致囊性纤维化、癌症和其他免疫功能低下健康状况患者的疾病严重程度增加和住院率升高。缺乏有效的抗生素导致人们对噬菌体疗法重新产生兴趣；然而，仍然非常需要特征明确的噬菌体，尤其是针对[细菌名称未给出]的噬菌体。针对一名患有败血症感染的肿瘤患者，我们从南加州污水进水口收集了18种噬菌体，它们对宿主菌株B28B表现出不同的噬菌斑形态。我们假设，当组合成鸡尾酒疗法时，基因多样化的噬菌体将产生不同的裂解感染动力学，与单独的单个噬菌体相比，这将增强细菌杀灭效果。我们鉴定出三个基因不同的噬菌体簇，并对每组中的一个代表进行了进一步研究和筛选以用于潜在的治疗用途。结果表明，在观察48小时时，三噬菌体鸡尾酒与单个噬菌体相比显著抑制了细菌生长。我们还评估了我们的三噬菌体鸡尾酒对46株[细菌名称未给出]菌株的裂解影响，以确定多噬菌体鸡尾酒是否具有扩大的宿主范围。我们的噬菌体仍然具有菌株特异性，感染了超过50%的测试菌株。在六种临床相关的[细菌名称未给出]菌株中，多噬菌体鸡尾酒增强了对细菌生长的抑制作用。这些发现表明，专门的噬菌体鸡尾酒可能是治疗对当前抗生素耐药的顽固性[细菌名称未给出]感染的有效途径。
