Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, College Park, MD, 20742, USA.
Department of Microbial Pathogenesis, Yale University School of Medicine, New Haven, CT, 06520, USA.
Nat Commun. 2018 Oct 25;9(1):4436. doi: 10.1038/s41467-018-06882-y.
Chronic bacterial infections on medical devices, including catheter-associated urinary tract infections (CAUTI), are associated with bacterial biofilm communities that are refractory to antibiotic therapy and resistant to host immunity. Previously, we have shown that Pseudomonas aeruginosa can cause CAUTI by forming a device-associated biofilm that is independent of known biofilm exopolysaccharides. Here, we show by RNA-seq that host urine alters the transcriptome of P. aeruginosa by suppressing quorum sensing regulated genes. P. aeruginosa produces acyl homoserine lactones (AHLs) in the presence of urea, but cannot perceive AHLs. Repression of quorum sensing by urine implies that quorum sensing should be dispensable during infection of the urinary tract. Indeed, mutants defective in quorum sensing are able to colonize similarly to wild-type in a murine model of CAUTI. Quorum sensing-regulated processes in clinical isolates are also inhibited by urea. These data show that urea in urine is a natural anti-quorum sensing mechanism in mammals.
医疗器械相关的慢性细菌感染，包括导管相关尿路感染（CAUTI），与对抗生素治疗具有抗性且能抵抗宿主免疫的细菌生物膜群落有关。此前，我们已经证明铜绿假单胞菌可以通过形成一种与已知生物膜胞外多糖无关的器械相关生物膜来引起 CAUTI。在这里，我们通过 RNA-seq 显示，宿主尿液通过抑制群体感应调节基因来改变铜绿假单胞菌的转录组。在存在尿素的情况下，铜绿假单胞菌会产生酰基高丝氨酸内酯（AHLs），但不能感知 AHLs。尿液对群体感应的抑制意味着在尿路感染过程中群体感应应该是可有可无的。事实上，在 CAUTI 的小鼠模型中，群体感应缺陷突变体能够与野生型相似地定植。尿素还抑制临床分离株中群体感应调节的过程。这些数据表明，尿液中的尿素是哺乳动物中天然的抗群体感应机制。
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