Designing phage cocktails to combat the emergence of bacteriophage-resistant mutants in multidrug-resistant Klebsiella pneumoniae. 2024

Seongjun Yoo, and Kang-Mu Lee, and Nayoung Kim, and Thao Nguyen Vu, and Ricardo Abadie, and Dongeun Yong
Department of Laboratory Medicine and Research Institute of Bacterial Resistance, Yonsei University College of Medicine , Seoul, South Korea.

In this study, we aimed to design a novel and effective bacteriophage cocktail that can target both wild-type bacteria and phage-resistant mutants. To achieve this goal, we isolated four phages (U2874, phi_KPN_H2, phi_KPN_S3, and phi_KPN_HS3) that recognized different bacterial surface molecules using phage-resistant bacteria. We constructed three phage cocktails and tested their phage resistance-suppressing ability against multidrug-resistant Klebsiella pneumoniae. We argue that the phage cocktail that induces resensitization of phage susceptibility exhibited superior phage resistance-suppressing ability. Moreover, we observed trade-off effects that manifested progressively in phage-resistant bacteria. We hypothesize that such trade-off effects can augment therapeutic efficacy. We also recommend collating phage host range data against phage-resistant mutants in addition to wild-type bacteria when establishing phage banks to improve the efficiency of phage therapy. Our study underscores the importance of phage host range data in constructing effective phage cocktails for clinical use.

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