Enhanced suppression of Stenotrophomonas maltophilia by a three-phage cocktail: genomic insights and kinetic profiling.

IF 4.1 2区 医学 Q2 MICROBIOLOGY
Antimicrobial Agents and Chemotherapy Pub Date : 2025-03-05 Epub Date: 2025-01-22 DOI:10.1128/aac.01162-24
Alisha N Monsibais, Olivia Tea, Pooja Ghatbale, Sage J B Dunham, Mirjam Zünd, Jennifer Phan, Karen Lam, McKenna Paulson, Natalie Tran, Diana S Suder, Alisha N Blanc, Cyril Samillano, Joy Suh, Hanna Atif, Ethan Vien, Ryan Nguyen, Allene Vo, Shane Gonen, David Pride, Katrine Whiteson
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引用次数: 0

Abstract

Stenotrophomonas maltophilia is an understudied, gram-negative, aerobic bacterium that is widespread in the environment and increasingly a cause of opportunistic infections. Treating S. maltophilia 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 S. maltophilia. 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 S. maltophilia 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 S. maltophilia 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 S. maltophilia 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 S. maltophilia infections resistant to current antibiotics.

通过三噬菌体鸡尾酒增强对嗜麦芽寡养单胞菌的抑制:基因组见解和动力学分析。
嗜麦芽窄养单胞菌是一种未经充分研究的革兰氏阴性需氧细菌,广泛存在于环境中,并日益成为机会性感染的原因。治疗嗜麦芽链球菌仍然很困难,导致囊性纤维化、癌症和其他免疫功能低下的健康状况患者的疾病严重程度增加和住院率升高。由于缺乏有效的抗生素,人们对噬菌体治疗重新产生了兴趣;然而,仍然非常需要具有良好特征的噬菌体,特别是针对嗜麦芽葡萄球菌的噬菌体。针对一名患有败血症感染的肿瘤患者,我们从南加州废水中收集了18个噬菌体,这些噬菌体对嗜麦芽葡萄球菌宿主菌株B28B表现出不同的斑块形态。我们假设,当组合成鸡尾酒时,基因多样化的噬菌体将产生不同的溶解感染动力学,与单独的单个噬菌体相比,这将增强细菌的杀伤能力。我们确定了三种遗传上不同的噬菌体簇,并从每组中进一步研究和筛选具有代表性的潜在治疗用途。结果表明,在观察48小时后,与单个噬菌体相比,噬菌体鸡尾酒显著抑制了细菌的生长。我们还评估了我们的噬菌体鸡尾酒对46株嗜麦芽葡萄球菌的裂解影响,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,并且感染了50%的测试菌株。在六种临床相关的嗜麦芽葡萄球菌菌株中,多噬菌体鸡尾酒增强了对细菌生长的抑制。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嗜麦芽葡萄球菌感染的有效途径。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
CiteScore
10.00
自引率
8.20%
发文量
762
审稿时长
3 months
期刊介绍: Antimicrobial Agents and Chemotherapy (AAC) features interdisciplinary studies that build our understanding of the underlying mechanisms and therapeutic applications of antimicrobial and antiparasitic agents and chemotherapy.
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