Aggarwal Surya D, Lokken-Toyli Kristen L, Weiser Jeffrey N
Department of Microbiology, New York University School of Medicine, New York, NY, USA.
Commun Biol. 2024 Dec 6;7(1):1628. doi: 10.1038/s42003-024-07176-4.
Using chromosomal barcoding, we observed that >97% of the Streptococcus pneumoniae (Spn) population turns over in the lung within 2 days post-inoculation in a murine model. This marked collapse of diversity and bacterial turnover was associated with acute inflammation (severe pneumococcal pneumonia), high bacterial numbers in the lungs, bacteremia, and mortality. Intra-strain competition mediated by the blp locus, which expresses bacteriocins in a quorum-sensing-dependent manner, was required for each of these effects. Bacterial turnover from the activity of Blp-bacteriocins increased the release of the pneumococcal toxin, pneumolysin (Ply), which was sufficient to account for the lung pathology. The ability of Ply to evade complement, rather than its pore-forming activity, prevented opsonophagocytic clearance of Spn enabling its multiplication in the lung, facilitating the inflammatory response and subsequent invasion into the bloodstream. Thus, our study demonstrates how an appreciation for bacterial population dynamics during infection provides new insight into pathogenesis.
利用染色体条形码技术，我们观察到在小鼠模型中，接种后2天内，超过97%的肺炎链球菌（Spn）群体在肺内更替。这种显著的多样性崩溃和细菌更替与急性炎症（严重肺炎球菌肺炎）、肺内高细菌载量、菌血症和死亡率相关。由blp位点介导的菌株内竞争以群体感应依赖的方式表达细菌素，这些效应中的每一个都需要这种竞争。Blp细菌素活性导致的细菌更替增加了肺炎球菌毒素肺炎溶血素（Ply）的释放，这足以解释肺部病理情况。Ply逃避补体的能力，而非其成孔活性，阻止了Spn的调理吞噬清除，使其能够在肺内繁殖，促进炎症反应并随后侵入血液。因此，我们的研究证明了对感染期间细菌群体动态的认识如何为发病机制提供新的见解。
