Schator Daniel, G Kumar Naren, Chong Samuel Joseph U, Jung Timothy K, Jedel Eric, Smith Benjamin E, Evans David J, Fleiszig Suzanne M J
Herbert Wertheim School of Optometry & Vision Science, University of California Berkeley, Berkeley, CA, USA.
Graduate Program in Infectious Diseases & Immunity, University of California Berkeley, Berkeley, CA, USA.
Nat Commun. 2025 Aug 11;16(1):7419. doi: 10.1038/s41467-025-62575-3.
Pseudomonas aeruginosa is a Gram-negative opportunistic pathogen able to cause life- and sight-threatening infections. Once considered an extracellular pathogen, numerous studies have shown it can survive intracellularly. Previously, we showed that P. aeruginosa inside cells can diversify into distinct subpopulations in vacuoles and the cytoplasm. Here, we report that the transition from vacuoles to cytoplasm requires collaboration with the extracellular subpopulation, through Ca influx enabled by their type III secretion system (T3SS) translocon pore proteins. Moreover, we show that collaboration among P. aeruginosa subpopulations can contribute to disseminating intracellular bacteria in vivo in a mouse infection model. This study lays the groundwork for future investigations into how cooperation between extracellular and intracellular bacteria within the host contributes to disease progression and persistence.
铜绿假单胞菌是一种革兰氏阴性机会致病菌，能够引发危及生命和视力的感染。它曾被认为是一种胞外病原体，但众多研究表明它能够在细胞内生存。此前，我们发现细胞内的铜绿假单胞菌可在液泡和细胞质中分化为不同的亚群。在此，我们报告，从液泡到细胞质的转变需要与胞外亚群协作，这是通过其三型分泌系统（T3SS）转运孔蛋白促成的钙离子内流实现的。此外，我们表明铜绿假单胞菌亚群之间的协作有助于在小鼠感染模型中在体内传播细胞内细菌。这项研究为未来探究宿主内胞外和胞内细菌之间的合作如何促进疾病进展和持续存在奠定了基础。
