Wall Lucas A, Wall Daniel
Department of Molecular Biology, University of Wyoming, Laramie, WY 82071, USA.
Microbiology (Reading). 2025 Jun;171(6). doi: 10.1099/mic.0.001575.
is commonly associated with the development of dental caries worldwide. Due to their specificity for , phage represents a promising avenue for future targeted therapeutic strategies. In this study, we investigated how phage resistance develops in . As a model phage, we used ɸAPCM01, which is known to infect a serotype e strain. We isolated and sequenced the genomes of 15 spontaneous resistant mutants and found that 10 had acquired novel clustered regularly interspaced short palindromic repeats (CRIPSR) spacers targeting the phage, with a total of 18 new spacers identified. Additionally, eight strains contained mutations in rhamnose-glucose polysaccharide biosynthetic genes, three of which also acquired spacers. Only the mutants exhibited defects in phage adsorption, supporting the role of these cell surface glycans as the phage receptor. Mutations in and the newly identified gene led to severe cell division defects and impaired biofilm formation, the latter of which was also shared by an mutant. Thus, mutations confer phage resistance but impose severe fitness costs, limiting pathogenic potential. Surprisingly, we found that ɸAPCM01 was capable of binding to and injecting its genome into UA159, a model serotype c strain. However, UA159 was resistant to infection due to an unknown post-entry defence mechanism. Consequently, ɸAPCM01 has the potential to infect both major serotypes associated with dental caries.
在全球范围内，它通常与龋齿的发展相关联。由于噬菌体对……具有特异性，噬菌体代表了未来靶向治疗策略的一个有前景的途径。在本研究中，我们调查了噬菌体抗性在……中是如何发展的。作为模型噬菌体，我们使用了ɸAPCM01，已知它能感染血清型e菌株。我们分离并测序了15个自发抗性突变体的基因组，发现其中10个获得了靶向噬菌体的新型成簇规律间隔短回文重复序列（CRIPSR）间隔序列，总共鉴定出18个新间隔序列。此外，8个菌株在鼠李糖 - 葡萄糖多糖生物合成基因中存在突变，其中3个也获得了间隔序列。只有……突变体在噬菌体吸附方面表现出缺陷，支持了这些细胞表面聚糖作为噬菌体受体的作用。……和新鉴定的基因……中的突变导致严重的细胞分裂缺陷和生物膜形成受损，后者在一个……突变体中也存在。因此，……突变赋予噬菌体抗性，但会带来严重的适应性代价，限制致病潜力。令人惊讶的是，我们发现ɸAPCM01能够与模型血清型c菌株UA159结合并将其基因组注入其中。然而，由于未知的进入后防御机制，UA159对感染具有抗性。因此，ɸAPCM01有可能感染与龋齿相关的两种主要血清型。
