Identification of a novel gene in Pseudomonas aeruginosa promotes persister formation by repressing translation and cell division

Bacterial persisters are dormant subpopulations that survive antibiotic killing without genetic change. These cells contribute to recalcitrant infections and serve as reservoirs for emergence of antibiotic resistance mutations. Pseudomonas aeruginosa is an opportunistic pathogen that is highly resistant to a variety of antibiotics. To characterize the global gene expression profiles of P. aeruginosa persister cells and resuscitating cells, we collected live cells after treatment with a lethal dose of meropenem and performed transcriptomic analysis. The PA2171 gene was upregulated in the persister cells and downregulated during resuscitation. Overexpression of PA2171 promoted persister formation. Affinity chromatography revealed that the PA2171 protein binds to ribosome and FtsZ, which are involved in translation and cell division, respectively. By measuring protein synthesis in live cells and an in vitro translation system, we demonstrated the direct role of PA2171 in repressing protein translation. Meanwhile, fluorescence microscopy and a light scattering assay demonstrated that PA2171 influences cell division by inhibiting FtsZ polymerization. Overall, our results revealed that PA2171 promotes persister formation by coordinating translational arrest and division blockade.