Center for Infection Biology, School of Basic Medical Sciences, Tsinghua University, Beijing 100084, China.
SXMU-Tsinghua Collaborative Innovation Center for Frontier Medicine, Shanxi Medical University, Taiyuan, Shanxi Province 030001, China.
Sci Adv. 2024 Sep 6;10(36):eadp5057. doi: 10.1126/sciadv.adp5057. Epub 2024 Sep 4.
Despite extensive knowledge on phage resistance at bacterium level, the resistance of bacterial communities is still not well-understood. Given its ubiquity, it is essential to understand resistance at the community level. We performed quantitative investigations on the dynamics of phage infection in biofilms. We found that the biofilms quickly developed resistance and resumed growth. Instead of mutations, the resistance was caused by unassembled phage tail fibers released by the phage-lysed bacteria. The tail fibers degraded the bacterial capsule essential for infection and induced spreading of capsule loss in the biofilm, and tuning tail fiber and capsule levels altered the resistance. Latent infections sustained in the biofilm despite resistance, allowing stable phage-bacteria coexistence. Last, we showed that the resistance exposed vulnerabilities in the biofilm. Our findings indicate that phage lysate plays important roles in shaping phage-biofilm interactions and open more dimensions for the rational design of strategies to counter bacteria with phage.
尽管人们对细菌层面的噬菌体抗性有了广泛的了解,但对细菌群落的抗性仍了解不足。鉴于噬菌体的普遍性,有必要在群落层面上了解抗性。我们对生物膜中噬菌体感染的动态进行了定量研究。我们发现生物膜很快产生了抗性并恢复了生长。这种抗性不是由突变引起的,而是由噬菌体裂解细菌释放的未组装的噬菌体尾部纤维引起的。这些尾部纤维降解了感染所必需的细菌荚膜,并诱导生物膜中荚膜损失的扩散,调节尾部纤维和荚膜的水平会改变抗性。尽管存在抗性,但潜伏感染在生物膜中得以维持,从而允许噬菌体和细菌稳定共存。最后,我们表明抗性暴露了生物膜中的弱点。我们的研究结果表明,噬菌体裂解物在塑造噬菌体-生物膜相互作用方面发挥着重要作用,并为设计对抗噬菌体细菌的策略提供了更多的维度。