Dalponte Anne, Filor Viviane, Lübke-Becker Antina, Fulde Marcus, Alter Thomas, Müsken Mathias, Bäumer Wolfgang
Institute of Pharmacology and Toxicology, School of Veterinary Medicine, Freie Universität Berlin, Berlin, Germany.
Institute of Microbiology and Epizootics, School of Veterinary Medicine, Freie Universität Berlin, Berlin, Germany.
BMC Microbiol. 2025 May 14;25(1):289. doi: 10.1186/s12866-025-04005-4.
Pseudomonas aeruginosa is an opportunistic pathogen that causes infections in both human and veterinary medicine, presenting significant challenges in treatment because of biofilm production and its intrinsic resistance. This problem is exacerbated by the increase in acquired antimicrobial resistance. Bacteriophage (phage) therapy has emerged as a promising alternative for treating infection classically treated with antibiotics, offering a targeted approach to combat this infection. This study aimed to evaluate the therapeutic potential of 7 phages, focusing on their suitability for treating canine infections, as well as their purification and safety analysis for therapeutic use.
Two self-isolated phages and five provided phages were analysed. All tested phages reduced bacterial load in vitro; however, their efficacy varied across different concentrations. The host range analysis revealed a spectrum between 9.8 and 68.6% of canine clinical P. aeruginosa isolates. In our in vitro tests 3 out of 7 phages were able to significantly reduce the biofilm biomass, achieving reductions up to 93.38%. The sequence analysis did not discover known virulence factors and genes connected to antimicrobial resistance mechanisms. The self-isolated phages were classified as lysogenic, whereas the other phages had a lytic infection cycle. Through the purification of the phages, high-titre phage preparations (> 10 PFU/ml) were generated with high stability for at least 1.5 years. The tested endotoxin units are below the regulatory limits.
Investigating phages as alternative treatment option seems promising with lytic phages covering a broad host range and a genomic potential for biofilm degradation. These findings support the development of phage cocktails as a targeted alternative for treating canine P. aeruginosa infections, particularly in cases of antibiotic resistance, and highlight the importance of selecting well-characterized lytic phages for therapeutic efficacy and safety.
铜绿假单胞菌是一种机会致病菌，可导致人类和兽医学感染，由于其生物膜的形成及其内在抗性，在治疗方面带来了重大挑战。获得性抗菌耐药性的增加使这一问题更加严重。噬菌体疗法已成为治疗传统上用抗生素治疗的感染的一种有前景的替代方法，为对抗这种感染提供了一种有针对性的方法。本研究旨在评估7种噬菌体的治疗潜力，重点关注它们对治疗犬类感染的适用性，以及它们用于治疗用途的纯化和安全性分析。
分析了两种自分离噬菌体和五种提供的噬菌体。所有测试的噬菌体在体外均降低了细菌载量；然而，它们的疗效在不同浓度下有所不同。宿主范围分析显示，犬临床铜绿假单胞菌分离株的感染范围在9.8%至68.6%之间。在我们的体外试验中，7种噬菌体中有3种能够显著降低生物膜生物量，减少幅度高达93.38%。序列分析未发现已知的毒力因子和与抗菌耐药机制相关的基因。自分离的噬菌体被分类为溶原性噬菌体，而其他噬菌体具有裂解感染周期。通过噬菌体的纯化，产生了高滴度的噬菌体制剂（>10 PFU/ml），具有至少1.5年的高稳定性。测试的内毒素单位低于监管限值。
研究噬菌体作为替代治疗选择似乎很有前景，裂解性噬菌体具有广泛的宿主范围和生物膜降解的基因组潜力。这些发现支持开发噬菌体鸡尾酒作为治疗犬铜绿假单胞菌感染的有针对性的替代方法，特别是在抗生素耐药的情况下，并强调选择特征明确的裂解性噬菌体以提高治疗效果和安全性的重要性。
