Institut Pasteur, Université Paris Cité, Biodiversity and Epidemiology of Bacterial Pathogens, Paris, France.
Department of Microbial Immune Regulation, Helmholtz Center for Infection Research, Braunschweig, Germany.
Microbiol Spectr. 2023 Aug 17;11(4):e0481222. doi: 10.1128/spectrum.04812-22. Epub 2023 Jun 20.
Klebsiella pneumoniae (Kp), a human gut colonizer and opportunistic pathogen, is a major contributor to the global burden of antimicrobial resistance. Virulent bacteriophages represent promising agents for decolonization and therapy. However, the majority of anti-Kp phages that have been isolated thus far are highly specific to unique capsular types (anti-K phages), which is a major limitation to phage therapy prospects due to the highly polymorphic capsule of Kp. Here, we report on an original anti-Kp phage isolation strategy, using capsule-deficient Kp mutants as hosts (anti-K phages). We show that anti-K phages have a broad host range, as the majority are able to infect noncapsulated mutants of multiple genetic sublineages and O-types. Additionally, anti-K phages induce a lower rate of resistance emergence and provide increased killing efficiency when in combination with anti-K phages. , anti-K phages are able to replicate in mouse guts colonized with a capsulated Kp strain, suggesting the presence of noncapsulated Kp subpopulations. The original strategy proposed here represents a promising avenue that circumvents the Kp capsule host restriction barrier, offering promise for therapeutic development. Klebsiella pneumoniae (Kp) is an ecologically generalist bacterium as well as an opportunistic pathogen that is responsible for hospital-acquired infections and a major contributor to the global burden of antimicrobial resistance. In the last decades, limited advances have been made in the use of virulent phages as alternatives or complements to antibiotics that are used to treat Kp infections. This work demonstrates the potential value of an anti-Klebsiella phage isolation strategy that addresses the issue of the narrow host range of anti-K phages. Anti-K phages may be active in infection sites in which capsule expression is intermittent or repressed or in combination with anti-K phages, which often induce the loss of capsule in escape mutants.
肺炎克雷伯菌（Kp）是一种人类肠道定植菌和机会致病菌，是导致全球抗菌药物耐药负担的主要因素之一。烈性噬菌体是定植和治疗的有前途的药物。然而，迄今为止分离到的大多数抗 Kp 噬菌体都高度特异性针对独特的荚膜类型（抗 K 噬菌体），这是噬菌体治疗前景的主要限制因素，因为 Kp 的荚膜高度多态性。在这里，我们报告了一种原始的抗 Kp 噬菌体分离策略，使用荚膜缺陷的 Kp 突变体作为宿主（抗 K 噬菌体）。我们表明，抗 Kp 噬菌体具有广泛的宿主范围，因为大多数噬菌体都能够感染多个遗传亚系和 O 型的非荚膜突变体。此外，抗 Kp 噬菌体诱导的耐药性出现率较低，与抗 Kp 噬菌体联合使用时可提高杀菌效率。此外，抗 Kp 噬菌体能够在被荚膜 Kp 菌株定植的小鼠肠道中复制，表明存在非荚膜 Kp 亚群。这里提出的原始策略代表了一种有前途的途径，可以规避 Kp 荚膜宿主限制障碍，为治疗开发提供了希望。
肺炎克雷伯菌（Kp）是一种生态普遍的细菌，也是一种机会致病菌，它导致医院获得性感染，并是导致全球抗菌药物耐药负担的主要因素之一。在过去几十年中，在使用烈性噬菌体作为替代或补充抗生素来治疗 Kp 感染方面取得的进展有限。这项工作表明了一种抗肺炎克雷伯菌噬菌体分离策略的潜在价值，该策略解决了抗 Kp 噬菌体宿主范围狭窄的问题。抗 Kp 噬菌体可能在荚膜表达间歇性或受抑制的感染部位或与抗 Kp 噬菌体联合使用时发挥作用，抗 Kp 噬菌体通常会诱导逃逸突变体失去荚膜。
