Surface-mediated bacteriophage defense incurs fitness tradeoffs for interbacterial antagonism
Dr. Ting, See-Yeun - March, 2025
Bacteria in polymicrobial environments face threats from phages, competing bacteria, and predatory eukaryotes. While bacterial defenses protect against these threats, their tradeoffs remain underexplored. Here, we investigated the fitness costs of phage resistance in Salmonella enterica, showing that phage-resistant variants suffer competitive disadvantages when co-cultured with rival bacteria. These strains exhibit lipopolysaccharide (LPS) deficiencies, increasing their susceptibility to type VI secretion system (T6SS)-mediated attacks. Mutational analysis and atomic force microscopy revealed that the long O-antigen of LPS acts as a protective shield against T6SS intoxication. Additionally, phages with LPS-targeting endoglycosidases can cleave the O-antigen, independently weakening bacterial competitiveness. Our findings highlight two distinct mechanisms by which phage-driven LPS modifications influence bacterial interactions, revealing tradeoffs that shape microbial competition in polymicrobial communities.
在多種微生物共存的環境中，細菌需應對來自其他物種的多重威脅。雖然細菌已演化出防禦機制以抵禦這些攻擊，但不同機制間的關係及其適應性權衡仍未被充分理解。本研究探討細菌對噬菌體抗性的適應性代價，發現某些抗噬菌體突變株雖可抵禦噬菌體感染，卻在與競爭菌共培時競爭力顯著下降。這些突變株表現出脂多醣缺陷，導致其更易受到其他細菌透過第六型分泌系統所介導的毒殺攻擊。突變分析與原子力顯微鏡觀察顯示，脂多醣的長鏈抗原可作為防禦屏障，有助於抵禦第六型分泌系統毒殺。此外，我們還發現帶有脂多醣水解內切酶的噬菌體可直接降解細菌表面的抗原鏈，進一步削弱細菌競爭力。本研究揭示了噬菌體介導的脂多醣修飾如何影響細菌間的交互作用，並強調其在多菌種環境中的適應性權衡。
本研究於 2025 年 3 月 10 日發表於《歐洲分子生物學組織期刊》（The EMBO Journal），第一作者為本院國際研究生分子與細胞學程博士候選人蔡佳恩與碩士級研究助理王豐錡，並與本院物理研究所黃英碩研究員合作。研究經費由本院前瞻計畫及國家科學及技術委員會「2030 跨世代優秀年輕學者計畫」支應。